Enhancement by TNF-alpha of reactivation and replication of latent herpes simplex virus from trigeminal ganglia of mice.

The influence of tumor-necrosis-factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukine-1 (IL-1) and IL-3 on the in vitro reactivation frequency and replication rate of trigeminal ganglia of mice latently infected with herpes simplex virus (HSV) strain KOS was studied. It could be demonstrated that TNF-alpha and possibility GM-CSF, but not IL-1 and IL-3, enhanced the reactivation frequency and replication of HSV. Interferon alpha/beta (IFN alpha/beta) prevented reactivation and replication.

Labormethoden zum Nachweis von Virusinfektionen

Bereits um 1880 standen Methoden zum Nachweis von bakteriellen Infektionen zur Verfugung: Nach Anfarbung waren die Erreger aufgrund ihrer Grose im Lichtmikroskop zu erkennen und konnten in Nahrmedien gezuchtet werden. Viren entzogen sich dieser Vorgehensweise, da sie deutlich kleiner sind und sich als obligate Zellparasiten in Nahrmedien nicht vermehren konnen. Zwar konnte man zur Jahrhundertwende bereits einige Virusinfektionen mit bestimmten Zellveranderungen und Ablagerungen im infizierten Gewebe in Verbindung bringen. Ein Beispiel sind die negrischen Einschlusskorperchen in Nervenzellen bei der Tollwuterkrankung. Eine spezifische Diagnostik war jedoch erst durch die Entwicklung der Meth…

Replication of herpes simplex virus type 1 and 2 in the medulla of the adrenal gland after vaginal infection of mice.

After vaginal infections of mice with neuroinvasive strains of herpes simplex virus type 1 and 2 (HSV-1, HSV-2) virus replicates in the epithelium of the vagina, in the paravaginal ganglia, in the spinal cord and finally in the brain and in the adrenal glands. However, viral antigens could be demonstrated only in the medulla of the adrenal glands but not in the cortex, as assessed by immunohistochemistry (IHC). HSV could not be isolated from liver, spleen, uterus, and ovaries. This contrasts to the intraperitoneal (i.p) route of infection with replication in different visceral organs including the adrenal gland's cortex.

Evidence for a multistep mechanism for cell-cell fusion by herpes simplex virus with mutations in the syn 3 locus using heparin derivatives during fusion from within

Addition of heparin-Na+ as well as related substances of high and intermediate MW (Arteparon and polyanion SP54) 3 h after infection inhibit fusion from within (FFWI) induced by HSV strains with mutations in the syn 3 locus only. The concentration of heparin-Na+ required to inhibit FFWI is 10-fold higher (1 mg/ml) than that needed to inhibit adsorption. Instead of fusion, cell rounding is observed. The effect is readily reversible. A low MW heparin disaccharide is ineffective. Neomycin, at a concentration of 8 mM, inhibits FFWI induced by all HSV-1 but not HSV-2 strains, whereas adsorption is inhibited at 3 mM. We conclude from our observations that cell-cell fusion (FFWI) induced by syn 3 …

Ribonuclease H levels in herpes simplex virus-infected cells.

Two forms of ribonuclease H (RNase H) have been identified both in uninfected and Herpes Simplex virus (HSV-)infected BHK cells. Identical RNase H species were detected in control- as well as in infected cells. RNase H I and II have not been found to be associated both with host cell DNA polymerase alpha and beta and HSV-induced DNA polymerase. Infection of BHK cells with HSV type 1 does not lead to a pronounced alteration of RNase H II activity but to an increase (3-fold) of the extractable RNase H I activity. RNase H I activity increases to a maximum between 8-10 hours p.i.; the bulk of HSV-DNA synthesis occurs between 6-8 hours p.i. From these experiments we draw the preliminary conclusi…

Vaginal infection of mice with HSV type 2 variant ER−: A new animal model for human primary genital HSV type 2 infections

Abstract Studying the pathogenesis of vaginal infections in mice with two variants of Herpes simplex virus type 2 (HSV-2) strain ER we observed that both variants ER+ and ER− caused severe vaginitis but only ER+ invaded the CNS leading to lethal neurological disease. In contrast, mice infected with ER− cleared the virus from the vagina and recovered from infection. ER+ and ER− expressed equal levels of thymidine kinase (TK) indicating a TK-independent difference in neurovirulence. Using the non-neurovirulent variant ER−, we were able to investigate humoral immune responses late after infection. Vaginal infection with ER− suppressed serum antibody formation after a secondary systemic HSV-1 i…

Two mutations in gB-1 and gD-1 of herpes simplex virus type 1 are involved in the "fusion from without" phenotype in different cell types.

Previous studies have shown that certain strains of herpes simplex viruses type 1 (HSV-1) are able to induce “fusion from without” (FFWO) which means no transcription or translation of the viral genome happens. The main determinants for FFWO in BHK cells are mutations in the C-terminal part of gB-1. But single mutations in this part of the genome are not sufficient to transfer the FFWO phenotype also to Vero cells. Here, we report that FFWO of HSV strains indeed need additional mutations in the N-terminal part of gD in order to produce the FFWO phenotype in BHK and Vero cells. By marker transfer we are able to show that loss of mutations in the N-terminal part of gD influences the ability t…

Cloning and expression of the complement receptor glycoprotein C from Herpesvirus simiae (herpes B virus): protection from complement-mediated cell lysis

Simian herpes B virus (SHBV) is the herpes simplex virus (HSV) homologue for the species MACACA: Unlike in its natural host, and unlike other animal herpesviruses, SHBV causes high mortality in accidentally infected humans. SHBV-infected cells, like those infected with HSV-1 and equine herpesvirus types 1 and 4, express complement C3 receptor activity. To study immunoregulatory functions involved in susceptibility/resistance against interspecies transmission, the SHBV glycoprotein C (gC(SHBV)) gene (encoding 467 aa) was isolated. Sequence analysis revealed amino acid identity with gC proteins from HSV-2 (46.9 %), HSV-1 (44.5 %) and pseudorabies virus (21.2 %). Highly conserved cysteine resi…

Autoradiographische Beobachtungen �ber den Einbau von3H-Uridin in herpesinduzierten Riesenzellen

Cytological studies indicate that Herpes induced polykaryocytes often contain normal appearing nuclei. Further, virus induced DNA-synthesis was absent in about 20% of the nuclei inside of giant cells as observed by autoradiography. On the other hand, RNA-synthesis seems to be inhibited in all nuclei of such cells as evidenced by reduced3H-uridin incorporation. It is concluded that nuclear RNA-synthesis is blocked by spreading of inhibitory factors.

Infections of susceptible and resistant mouse strains with herpes simplex virus type 1 and 2.

The spread of HSV of type 1 and 2 was investigated after intraperitoneal, intraplantar and intracerebral infections of resistant (C57/bl) and susceptible (NMRI) mice. The virus spreads after i.p. infection to the spleen and the liver to the same extent in both strains of mice. However, virus is eliminated earlier in resistant mice. Intracerebral infections revealed a peculiar type of resistance of C57/bl mice especially for type 2 of HSV. HSV multiplies in the thymus at the early stage of infection and can be detected in this organ in sick mice of NMRI strain. HSV-1 and 2 can be detected in the spinal cord of C57/bl mice without sickness or death of these animals.

Herpes simplex virus type 1 and 2 in the adrenal glands: Replication and histopathology

The adrenal glands were shown to be the most severely infected organs in the early phase of HSV-1 infections (up to 10 days p.i.) after i.p. infections in mice. Virus could be isolated from the adrenal glands as early as one hour after infection with pathogenic and apathogenic strains. Infection of the adrenal glands is a result of viremia. The content of HSV-1 (5 strains) was much higher in the adrenals than in spleen and liver. It peaked at 3-4 days p.i. compared to 1-2 days in spleen and liver. Only strain 17 syn+ produced low tissue titres in the adrenal glands. Morphologic alterations by HSV-1 infections commenced with distinct foci 2 days after infection in the zona fasciculata, detec…

Pathogenese der Viruskrankheiten

Der Begriff Pathogenese bezeichnet die Lehre von der Ausbreitung der Viren im Organismus und den Mechanismus der Krankheitsentstehung. Die Bezeichnung Pathogenitat eines Virus bezieht sich auf seine krankmachende Wirkung fur eine Spezies, z. B. den Menschen. Allerdings kann die Virulenz der Mitglieder einer Virusspezies fur den Menschen variieren, z. B. sind Impfstoffviren nahezu avirulent.

Die Hemmung der Riesenzellbildung durch das sogenannte Compound 48/80 nach der Infektion mit dem Herpesvirus hominis

Es wurde uber die Wirkung des Histamin-Liberators Compound 48/80 auf die Phasen der Synthese des Herpesvirus hominis und auf normale Zellstoffwechselprozessein vitro berichtet.

Factors influencing the interaction of herpes simplex virus glycoprotein C with the third component of complement.

The factors influencing the interaction of herpes simplex virus (HSV) glycoprotein C (gC) with the third component of complement (C3) were investigated in this study. The ability of gC of HSV type 1 (gC-1) to bind to the C3b fragment of C3 was found to be influenced by cell specific processing of gC-1 in a different manner, binding being remarkably enhanced in some cell lines following removal of sialic acid residues. Testing several intertypic recombinants of HSV we found that only strains expressing gC-1 exhibited binding to C3b, even though their genome consisted mainly of HSV-2 sequences in some recombinants. Expression of type-2 glycoproteins gB, gD, gE, gG, gH, and gI did not alter th…

Akute und chronische Virus-Erkrankungen des Zentralnervensystems

Virale Erkrankungen konnen akut als Meningitis, Enzephalitis und Myelitis verlaufen. Da diese Lokalisationen nicht immer streng abgrenzbar sind, werden auch die Bezeichnungen Meningoenzephalitis und Enzephalomyelitis gebraucht. Alle viralen Infekte zeichnen sich durch ein lymphozytares Infiltrat und Lymphozyten im Liquor aus, dem eine granulozytare Phase vorausgehen kann. Ca 50% der Falle bleiben atiologisch ungeklart. Eine Abgrenzung der einzelnen Er- krankungen erfolgtauf Grund des klinischen Bildes, der Anamnese (Zeckenstich, Hundebisse, Auslandsreisen) sowie der virologischen Diagnostik.

LEVELS OF RIBONUCLEASE H IN CELLS INFECTED WITH HERPES SIMPLEX VIRUS TYPE1

Erworbenes Immundefektsyndrom (AIDS)

1981 fielen schwere Immundefizienzzustande bei jungen Homosexuellen mit Kaposi Sarkom und Pneumonien durch Pneumozystis carinii auf, Erkrankungen, die bis dahin nur bei alten Personen oder Fruhgeborenen beobachtet wurden. Dieser Erkrankungskomplex wurde erworbenes Immunmangelsyndrom (AIDS) benannt. Spater wurde noch eine Erkrankung des ZNS (AIDS-Demenz) dem HIV zugeordnet. 1983/84 isolierten L. Montagnier und R. C. Gallo das HIV1, spater wurde in Westafrika das HIV2 nachgewiesen. Die Infektionen haben sich zu einer Pandemie ausgeweitet, zur Zeit (Ende 1997) sind etwa 30–40 Mio Personen infiziert und 11 Mio Personen an AIDS erkrankt bzw. gestorben. Vor allem in Afrika, Indien, Sudostasien un…

Definition, Struktur und Systematik der Viren

Viren sind als komplexe Makromolekule obligat intrazellulare Parasiten. Sie sind ultrafiltrierbar, im Lichtmikroskop nicht darstellbar und auf kunstlichen Nahrboden nicht zuchtbar. Sie vermehren sich nur in lebenden Zellen. Sie teilen sich nicht und wachsen nicht, sondern werden aus vorgeformten Untereinheiten montiert. Sie geben der Zelle Synthese-Anweisungen fur Virusbestandteile, die zu neuen Partikeln montiert werden („Genpakete mit todlichem Inhalt“). Ihre Replikation ist abhangig von einem zweckmasig auf die Bedurfnisse der Virusreplikation zugeschnittenen Zellstoffwechsel. Hierfur liefert das Virus ein Programm, das durch viruskodierte Proteine gesteuert wird.

The human autoantigen La/SS-B accelerates herpes simplex virus type 1 replication in transfected mouse 3T3 cells.

SUMMARY Permanently transfected mouse cell lines which expressed different levels of the human autoantigen La/SS-B were infected with different strains of herpes simplex virus type 1, including the strains ANG, HSZP, 17syn+ and HFEM. During infection the localization of the human La protein was followed using an anti-La MoAb, which recognized only the human La protein but did not cross-react with either the endogenous mouse La protein or any viral encoded protein. After infection La protein was transported from the nucleus to the cytoplasm. The time course of translocation was dependent on the amount of human La protein expressed in the respective cell line. Moreover, acceleration of viral …

Viren mit einzelsträngigem RNA-Genom und doppelsträngiger DNA als Zwischenprodukt

Retroviren wurden vor etwa 100 Jahren zum ersten Mal beschrieben: Nachdem Vilhelm Ellermann und Oluf Bang bereits 1908 die Mauseleukamie durch Ultrafiltrate ubertragen hatten, entdeckte Peyton Rous 1911, dass er mit ultrafiltrierten Extrakten aus Geflugelsarkomen diese Tumorerkrankung auf gesunde Huhner ubertragen konnte. Er erhielt hierfur 1966 den Nobelpreis, und das in den Extrakten enthaltene Retrovirus wurde nach ihm Rous-Sarkomvirus genannt. Einen weiteren Hinweis auf die Verursachung von Tumorerkrankungen durch Retroviren erhielt John J. Bittner 1936 bei seinen Untersuchungen zur Entstehung von malignen Milchdrusenerkrankungen der Maus: Er beschrieb das MMTV (Maus-Mammatumor-Virus) a…

Transformation und Tumorbildung

Schon fruh erkannte man, dass Viren bei Tieren Tumorerkrankungen hervorrufen konnen. Bereits 1911 beschrieb Peyton Rous, dass Viren bei Geflugel Sarkome verursachen. Das verantwortliche tumorauslosende Virus wurde spater nach ihm Rous-Sarkomvirus benannt. In den folgenden Jahrzehnten entdeckte man eine Vielzahl von Viren, die bei Geflugel und Nagetieren unterschiedliche Krebserkrankungen wie Lymphome, Sarkome und Karzinome auslosen konnen. Viele von ihnen gehoren zur Familie der Retroviridae und wurden den Gattungen der α-, β- und γ-Retroviren zugeordnet. Die Mehrzahl dieser Erreger wurde aus Inzuchtstammen der jeweiligen Tierarten oder aus Zellkulturen isoliert; unter naturlichen Bedingung…

Inhibition of the herpes simplex virus-coded thymidine kinase-complex by 9-?-D-arabinofuranosyladenine 5?-monophosphate (ara-AMP) and 9-(2-hydroxyethoxymethyl)guanine-monophosphate (acyclo-GMP)

The thymidine kinase-complex isolated from herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) is associated with the following enzyme activities: ATP:dThd (dCyd) deoxypyrimidine kinase, ATP:dTMP thymidylate kinase, ADP:dThd- and AMP:dThd5′-phosphotransferase. In kinetic experiments it is shown that ara-AMP inhibits AMP:dThd- and ADP:dThd phosphotransferase activity, while acyclo-GMP impairs ADP:dThd phosphotransferase reaction only; the inhibition was found to be non-compertitive. The functional subunit ATP:dThd kinase was not affected by either compound.

Analysis of the TK enzyme complex induced by HSV types 1 and 2 by means of isoelectric focusing and polyacrylamide gel electrophoresis.

Recently we have described that the Herpes simplex virus (HSV)-induced thymidine kinase (TK) induces AMP- and ADP-dThd-5'-phosphotransferase activities. We now demonstrate the heterogeneity of the described activities in isoelectric focusing experiments and polyacrylamide gel electrophoresis. A TK--mutant of HSV type 1 fails to induce these activities. The activities of the type 1 enzyme complex was neutralized by an anti-HSV-serum. The TK-enzyme complex expressed in LTK--cells transformed to a TK+-phenotype by sheared HSV-1 DNA was compared with the wild type TK complex in isoelectric focusing experiments. Additionally we demonstrate that the HSV type 1 enzyme complex has thymidylate kinas…

Intracellular distribution of the La antigen in CV-1 cells after herpes simplex virus type 1 infection compared with the localization of U small nuclear ribonucleoprotein particles.

The La antigen is known to associate, at least transiently, with a series of small nuclear and cytoplasmic ribonucleoprotein particles (snRNPs and scRNPs), e.g. U1 and U6 snRNPs. In CV-1 cells a monoclonal antibody (MAb), directed against the La protein (La1B5), immunostained intranuclear speckles. These speckles were found to co-localize with speckles that were stained by MAbs directed against either all U snRNPs or only against U1 snRNPs. Two h after infection of CV-1 cells with herpes simplex virus type 1 (HSV-1) (strain HFEM) the staining of nuclear speckles with the anti-La MAb disappeared and the La protein was found quantitatively in the cytoplasm. In contrast nuclear speckles remain…

Single amino acid substitutions in the glycoprotein B carboxy terminus influence the fusion from without property of herpes simplex virus type 1.

Syncytial mutations of herpes simplex virus type 1 (HSV-1) strains ANG, ANG path, HFEM, tsB5 and HSZP cause extensive cell fusion and were mapped to the cytoplasmic domain of glycoprotein B (gB), within the syn 3 locus. These strains are so far the only ones which show the phenotype ‘fusion from without’ (FFWO): 60 min after infection with high m.o.i., cells in a tissue culture are fused without transcription and translation of the viral genome. In this report we detected, using the recombinants 27/III and K-7, that an amino acid exchange from Ala to Val at aa position 854 of gB is the main determinant for FFWO activity of strains ANG, ANG path and recombinant K-7. The transfer of this muta…

Immunadhärenz zum Nachweis virusspezifischer Antikörper und Antigene

Nach dem Prinzip der Immunadharenz-Reaktion wurde eine Methode ausgearbeitet, die einen Nachweis von virusspezifischen oder zellspezifischen Antigenen auf oder in den Membranen von lebenden Zellen in vitro gestattet: Immunadharenz-Hamadsorption.

Induction capacity and influence of dThdMP on thymidine kinase activity of type 1 and 2 strains of herpes simplex virus

The thymidine kinase inducing ability of 104 strains of herpes simplex virus was studied comparatively. A pronounced relationship was established between induction of the enzyme and the serotype of the strains. As a rule, the strains of serotype 2 are weaker inducer of dThd- and dCyd-kinase activity than serotype 1 strains. A certain parallelism exists between induction of both enzymes, however the activity of the thymidine kinase increases after infection with herpes simplex virus 4--5 times more than that of the dCyd-kinase. Adaptation of the strains to cell cultures only slightly modifies the inducing ability of the herpes simplex virus strains. The thymidine kinase activity induced by H…

Papillom- und Polyoma-Viren

Zwei Virusfamilien, Papillom-Viren und Polyoma-Viren, wurden fruher als Papova-Viren (Papillom, Polyoma, Vacuolating Agent) zusammengefasst und sind im Tierreich weit verbreitete epitheliotrope DNA-Viren. Beim Menschen rufen Papillom-Viren gutartige Warzen, Kondylome und bosartige Karzinome hervor. Bei Immundefizienz verursacht eines der Polyoma-Viren, JC, eine Enzephalopathie (PML), wahrend BK-Virus bei Transplantatempfangern eine Nephropathie und hamorrhagische Zystitis verursachen kann. Die Papova-Viren werden eingeteilt in: — Gruppe A: Menschliche Papillom-Viren (HPV) sowie Rinder- und Kaninchenpapillom-Virus. — Gruppe B: Polyoma-Virus der Maus, das vakuolisierende Virus (Simian-Virus (…

DNA-dependent DNA polymerase pattern in noninfected and herpesvirus infected rabbit kidney cells.

In this paper we report on a DNA-dependent DNA polymerase produced in herpesvirus infected cells which is not present in virions. It differs from the polymerases of noninfected cells by its molecular weight as well as by its insensitivity to cytosine arabinoside triphosphate (ara-CTP).

Viren mit einzelsträngigem RNA-Genom in Plusstrangorientierung

Heute sind acht Virusfamilien bekannt, deren Vertreter eine einzelstrangige RNA in Plusstrangorientierung besitzen: Die Picornaviridae, Caliciviridae, Astroviridae und Hepeviren verfugen uber Capside, die keine Hullmembran aufweisen, wohingegen die Flaviviridae, Togaviridae, Arteriviridae und Coronaviridae durch membranumhullte Partikel gekennzeichnet sind. Allen gemeinsam ist, dass sie ihre Genome als mRNA verwenden und davon ein oder mehrere Polyproteine synthetisieren, die im weiteren Verlauf durch virale oder auch zellulare Proteasen in Einzelkomponenten gespalten werden. Die Viren verfugen uber eine RNA-abhangige RNA-Polymerase, welche die Plusstrang-RNA sowie die als Zwischenprodukte …

Characterization of fusion from without induced by herpes simplex virus

The process of fusion from without (FFWO) induced by herpes simplex virus (HSV) was analyzed by using various inhibitors and compared to fusion from within (FFWI). The fate of certain elements of the cytoskeleton after FFWO was also investigated. Our experiments demonstrate FFWO as a very suitable system for study of early virus-cell interactions. Zn++ ions proved inhibitory for penetration whilst pretreatment of cells with Ca++ ions before infection enhanced FFWO activity. Dissociation of penetration from the fusion process itself was possible by use of Zn++ ions, low pH-treatment and antiserum on the one hand and N-ethylmaleimide and cytochalasin D on the other. Penetration itself needs o…

Cyclosporin A resistance of herpes simplex virus-induced "fusion from within" as a phenotypical marker of mutations in the Syn 3 locus of the glycoprotein B gene.

We here report research in which nine strains of Herpes simplex virus (HSV) with fusing activity were investigated in order to establish precise phenotypical markers of mutations in the carboxy terminus of glycoprotein B (gB). The gene region encoding the carboxy terminus of gB was isolated, then cloned, and finally sequenced. Our investigation showed that seven strains have different mutations in the syn 3 locus. We observed no base difference in the gB gene region encoding the carboxy terminus of gB of two other strains. Strains with a mutation in the carboxy terminus of gB induced fusion from within (FFWI) in the presence of Cyclosporin A (CyA) at a concentration up to 150 µM. There are …

Poliomyelitis und Enteroviren

Die Kinderlahmung oder Poliomyelitis wurde 1840 durch Heine und Medin erstmals beschrieben. Mit der Entwicklung des Salk- und des Sabin-Impfstoffes wurde die Polio weitgehend zuruckgedrangt und wird in Mitteleuropa jetzt nur noch nach Einschleppung gesehen.

DNS-, RNS- und Proteinsynthese und ihre Relation zur Riesenzellbildung in vitro nach Infektion mit Herpesvirus hominis

In der vorliegenden Arbeit wird uber die zeitlichen Relationen von Virus-DNS-Synthese einerseits und Riesenzellbildung, Proteinsynthese sowie virusbedingter Hemmung der Zell-RNS-Synthese andererseits berichtet. Die Ergebnisse wurden autoradiographisch durch Einbau von Tritium-markiertem Thymidin, Uridin und Aminosauren in Kombination mit zeitlich abgestuften Gaben von Actinomycin C, Actidion oder pFPA gewonnen.

Asymptomatic vaginal herpes simplex virus infections in mice: virology and pathohistology

One of the causes of genital tract infections in humans are herpes simplex virus types 1 and 2 (HSV-1, HSV-2). Although primary and recurrent infections can be clinically apparent and in part very serious, many infections are asymptomatic and result only in temporary genital shedding of virus (recurrences). During our investigations of vaginitis, strain IES of HSV-1 produced an asymptomatic infection. Replication in the murine vaginal (vag.) epithelium as well as antibody formation after vag. infection was comparable to those of survivors after infection with highly virulent strains. Titration of liver, spleen, ovaries, adrenal glands spinal cord, or brain after vag. IES infection revealed …

Riesenzellbildung und virusspezifische antigene bei herpesvirus hominis: Informationsflu� von der eltern-DNS

Es wird uber den Einflus von Cytosin-Arabinosid, Hydroxy-Urea und von Mitomycin C auf die Entstehung membranstandiger oder extrahierbarer Antigene, auf die Riesenzellbildung sowie auf die Herpesvirus-bedingte Hemmung der Zell-RNS-Synthese berichtet. Durch die Verabreichung der drei Substanzen wird die Reduplikation der DNS des eingedrungenen Virus vollig blockiert. Trotzdem lassen sich die Phanomene der Riesenzellbildung, der Virus-Antigen-Synthese und der Synthesehemmung der Zell-RNS in vollem Umfange nachweisen.

Pathogenesis of HSV-1/2 induced vaginitis/vulvitis of the mouse: dependence of lesions on genetic properties of the virus and analysis of pathohistology

A scoring system for herpes simplex virus (HSV) induced vaginitis/vulvitis in Balb/c mice was delineated from vaginal infections. Four degrees of vaginitis/vulvitis could be distinguished after infection with suitable strains of HSV despite nearly identical replication rates. The time course of replication, inflammation and pathohistology was compared further. Grade 0 was defined by lack of symptoms despite presence of strong replication, which was detectable at days 3-6. Focal necrotic lesions of the epithelial layer were present containing HSV-specific antigens. DNA could be detected by hybridization only in the outer zone of these areas. At day 6 these zones began to be re-epithelialized…

Viren mit doppelsträngigem, segmentierten RNA-Genom

Reoviridae und Birnaviridae verfugen uber ein segmentiertes, doppelstrangiges RNA-Genom. Ahnliche molekulare Eigenschaften findet man bei Pflanzenviren, wie beispielsweise den Partitiviren. Das Genom der Birnaviren, von denen es keine humanpathogenen Vertreter gibt, verfugt uber zwei Genomsegmente. Bei den Reo-viren findet man dagegen ein aus neun bis zwolf RNA-Segmenten bestehendes Genom. Sie sind weltweit verbreitet und verursachen in Menschen und Tieren zum Teil schwere Erkrankungen

Influence of double infections on the induction of thymidine kinase by UV-irradiated herpes simplex virus types 1 and 2 and pseudorabies virus

Simultaneous infection of primary rabbit kidney cells with HSV type 1 TK+ and a TK- strain results in a mutual influence of both viruses on the induction of thymidine kinase (TK). TK+ virus has an enhancing and TK- virus a depressing effect on TK induction by a superinfecting TK+ virus. The enzyme induction depends on the ratio of multiplicities of both viruses. The mutual influence on TK induction depends further on the time of addition of the superinfecting virus: the effect of the second virus can still be observed when given 6 hours after primary infection. Identical phenomena can be observed using combinations with HSV type 2 or Pseudorabies viruses. The ability of HSV to induce TK is …

Die Evolution der Viren

Viren sind aufgrund ihrer kurzen Generationszeit, der grosen Zahl von Nachkommen, die sie im Infektionsverlauf produzieren, und nicht zuletzt aufgrund ihrer einfachen Struktur ideale Objekte zum Studium von Evolutionsprozessen. Viren mussen sich standig den Bedingungen ihres Wirtes oder ihrer Wirtspopulationen anpassen, sodass Mechanismen der Selektion experimentellen Ansatzen zuganglich sind. Dabei spielen unterschiedliche Kriterien, wie die antigene Diversitat, das Ausmas der Virusausscheidung, der Grad der Virulenz und viele andere Faktoren eine wichtige Rolle. Die vollstandige Adaptation eines Virus an seinen Wirt, welche in eine moglichst geringe Virulenz des Infektionserregers mundet,…

Microtubules and microfilaments in HSV-Infected rabbit-kidney cells.

In rabbit kidney cells infected with strains of Herpes simplex virus producing either cell-rounding or polycaryocytosis. Vinblastine induced paracrystals. This could be shown by phase-contrast- and electron-microscopy. Infections were done under one-step-growth conditions or at low MOI. 90 per cent noninfected cells contained stress fibers as detected by Servablue R250-staining. Shortly after recruitment into polycaryocytes, stress fibres of normal length appearing in criss-cross arrangement can be seen in the periphery of these cells. Later they polymerize to very long fibers and finally they are partially destroyed. The time of destruction depends on the MOI employed. By using Actinomycin…

Colonization of adrenal glands and ovaries of mice by HSV-2 variants

HSV-2 strain ER was shown to consist of variants with different pathogenic phenotype: Variant ER+ replicates to high titers in the adrenal glands and the ovaries but much less in the spleen; the testes were not colonized. ER+ migrates to the spinal ganglia and is highly neuroinvasive after i.p. inoculation. Variant ER- replicates 100-1,000 fold less in the adrenal glands and the ovaries, but proceeds to the spinal ganglia without invading the CNS. However, both variants are highly neuropathogenic after direct i.c. injection. We conclude that neuropathogenicity, neuroinvasiveness and the ability to replicate in the adrenal glands as well as ovaries are each determined by different sets of ge…

Orthomyxo-Viren: Influenza

Die Verursacher der Influenza (“Grippe„), Influenza-Virus A, B, C, stellen Genera in der Familie der Orthomyxo-Viren dar und kommen in vielen, sich abwechselnden Subtypen vor. 1918 hat die Pandemie der “Spanischen Grippe„ 50 Mio. Todesopfer gefordert. Die Morbiditat betrug 25–40%, dabei ist in Wien z. B. der Maler Egon Schiele gestorben. Weitere Pandemien 1957 und 1963 waren von geringerer, aber signifikanter Letalitat (“Ubersterblichkeit„) begleitet. In den USA sterben alljahrlich im Durchschnitt der Jahre etwa 36 000 Personen an der Influenza, in Deutschland 8000–12000.

Thymidine-, uridine- and choline-kinase in rabbit kidney cells infected with herpesvirus hominis, type I and II.

Data are presented about the activity of the thymidine-, uridine- and choline-kinase after infection with 21 strains ofherpesvirus hominis of serotype I or II in rabbit kidney cells. Type I strains increase the activity of the thymidine-kinase 15–20 fold over the controls, whereas the type II strains demonstrate a moderate activity, the level of the enzyme is increased 2–5 fold. One giant cell forming strain exhibits unusual properties, the TK activity decreases in correlation to the controls. The uridine- and choline-kinases induce the respective enzymes in different manner. The strains tested are divided into 5 groups depending upon the activity of the enzymatic activity. The implications…

Inhibition of herpesvirus DNA synthesis by 9-beta-D-arabinofuranosyladenine in cellular and cell-free systems.

9-beta-D-Arabinofuranosyladenine 5'-triphosphate (ara-ATP) is an inhibitor both of DNA polymerase-alpha and -beta from noninfected rabbit kidney cells and of the DNA-dependent DNA polymerase induced by herpes simplex virus Type 1 (strain IES). The studies were performed with partially purified enzymes, and each of the different polymerase preparations contained only one DNA-dependent DNA polymerase species. These enzymes were inhibited in a competitive manner. The HSV-induced DNA-dependent DNA polymerase was 39-fold more sensitive to ara-ATP than was cellular DNA polymerase-beta and 116-fold more sensitive than cellular DNA polymerase-alpha. The affinity of the HSV-induced enzyme for ara-AT…

Colonization of adrenal glands and ovaries of mice by variants of HSV 1 and 2

The herpes simplex virus (HSV)-infected mouse model was used to correlate histopathological lesions in adrenal glands and ovaries with the localisation of viral nucleic acids and viral antigens, employing in situ hybridization and immunohistochemistry. In the adrenals, the lesions were mainly restricted to the zona fasciculata and the zona reticularis, sometimes extending to the medulla. In the ovaries, lesions were detected in follicles and in the stroma. During the course of infection, HSV nucleic acids could be detected earlier than HSV proteins. Next to the center of necrotic foci mainly HSV proteins were detected, whereas peripheral cells were found to contain viral nucleic acids. In s…

Inhibition of giant cell formation by compound 48/80 after infection with herpesvirus hominis

Choline kinase has been found to be a soluble enzyme with a molecular weight of 105,000 in the cytoplasm of primary rabbit kidney cells. It has been purified 150-fold. It was investigated whether the inhibiting effect of Cpd 48/80 on virus-induced giant cell formation is due to interference with this enzyme. Cpd 48/80-dimer was shown to inhibit the choline kinase activityin vitro without a concomitant inhibition of giant cell formation. Likewise, another competitive inhibitor of choline kinase, purinyl-6-histamine, does not prevent giant cell formation. This finding suggests that there is no correlation between choline kinase activity and giant cell formation.

Microtubules and intermediate filaments of herpes simplex virus infected cells.

The fate of microtubules and of vimentin or keratin containing intermediate filaments during infection with fusion or rounding producing strains of herpes simplex virus (HSV) was investigated. Microtubules polymerize early after fusion of cells. However, they do not reconstitute 6–7 hours post infection (p.i.) after release of a colcemid block. Keratin and vimentin are maintained around the original nucleus still inside of recruited cells in the polykaryocyte. Cells of fibroblastic and epithelial origin fuse. Inside of polykaryocytes keratin or vimentin containing fibers seem to polymerize. Keratin is to be found in invaginations in the nuclei surrounded by the inner layer of the nuclear me…

Differentiation of herpes simplex virus-induced fusion from without and fusion from within by cyclosporin A and compound 48/80.

Treating strains of herpes simplex virus (HSV) in culture with either cyclosporin A or compound 48/80, allowed the strains to be divided into two groups. Group 1 contains the strains ANG and HFEM of HSV-1 and Lux syn (HSV-2) producing fusion from within (FFWI) and fusion from without (FFWO). Cyclosporin A fails to inhibit both types of fusion at concentrations up to 100 microM. Strains ANG and HFEM belong to the syn 3 marker locus group identified for HSV-1. Group 2 contains all other fusion-producing strains of HSV tested so far. Cyclosporin A inhibits FFWI at concentrations as low as 10 to 20 microM. These strains belong to the syn locus marker groups 1, 2, 4 and 5. From the fact that mut…

Mixed vaginal infections of Balb/c mice with low virulent herpes simplex type 1 strains result in restoration of virulence properties: vaginitis/vulvitis and neuroinvasiveness.

Vaginal infections of BALB/c Ann mice with herpes simplex virus type 1 (HSV-1) were studied. Mice were inoculated with virulent strains ANG path and 17 syn+ or low-virulent recombinant strains 27/III and 17-syn3 that differ from parental strains in their glycoprotein B (gB) gene sequences. When low-virulent strains were inoculated separately, no vaginitis/vulvitis was produced despite replication in the vagina. In contrast, after coinfection of mice with the two low-virulent strains, vaginitis/vulvitis was produced and virus could be recovered from the central nervous system (CNS). Two of the CNS isolates produced vaginitis/vulvitis, neuroinvasiveness and death of mice after vaginal infecti…

Involvement of actin-containing microfilaments in HSV-induced cytopathology and the influence of inhibitors of glycosylation.

Two and a half hours after infection with a high dose of different strains of HSV-1 which induce rounding of cells, breakdown of actin containing microfilaments can be observed. At the periphery of the cell, actin containing knob-like protuberances were visible. Later on, actin seems to be located exclusively on the surface of cells. Observations were done by immunofluorescence microscopy, scanning electron-microscopy and immunoperoxidase staining of ultrathin sections. The envelope of HSV appears to be stained by anti-actin. Strain IES produces rounding of cells at a high dose of infection before fusion proceeds at 37 degrees C. Similar alterations were not observed with the fusing strains…

Relationship between HLA I surface expression and different cytopathic effects produced after herpes simplex virus infection in vitro.

In the present study, we investigated the effects of herpes simplex virus (HSV) infection on the expression of HLA class I antigens and beta 2-microglobulin in human fibroblasts. The mRNA abundance for HLA class I was shown to be strongly reduced after infection with HSV strains either producing cell rounding or fusion from within (FFWI), however, HLA class I expression on the surface of cells is strongly reduced only after appearance of FFWI. Using a ts mutant (ts 78R) or CyA in combination with a fusion from without (FFWO) inducing strain of HSV, this loss of HLA class I antigens is assumed to be correlated to the rearrangement of the cell membrane during the fusion process itself as a la…

Identification and properties of the cell membrane bound leucine aminopeptidase interacting with the potential immunostimulant and chemotherapeutic agent bestatin.

Bestatin was found to be a competitive inhibitor (with respect to the Leu-NA substrate) not only of the isolated microsomal and cytosolic leucine aminopeptidases (Leu-APm and Leu-APc) but also of the aminopeptidases (APs) present in membrane preparations (from mouse liver) and on the cell surface of L5178Y cells. Kinetic parameters indicate that cellular AP is identical to Leu-APm. To rule out the possibility that AP-B is involved in the inhibition reactions, comparable studies with amastatin were performed. Electrophoretical studies revealed the solubilized cell membrane bound AP to co-migrate with Leu-APm in polyacrylamide gels. The activity of the separated membrane AP was inhibited by b…

The effect of arabinofuranosyl-cytosine upon the synthesis of herpesvirus hominis Electron microscopic observations in relation to viral DNA-synthesis

The paper describes experiments about the degree of dependency of capsid, envelope and antigen synthesis byherpesvirus hominis upon viral DNA synthesis. The DNA synthesis has been blocked by different doses of Ara-C and the remnant DNA-synthesis has been measured by [3H]-thymidine incorporation after CsCl-density gradient centrifugation. Electron microscopic studies were done in parallel after incubation of infected cells with different doses of Ara-C. Finally, antigens were prepared after infection without and with added Ara-C. Increasing amounts of Ara-C inhibited the synthesis of viral DNA and infective particles. 1.5 μg Ara-C reduced the remaining incorporation into DNA to about less th…

Biological activity of 2-phenylethanol and its derivatives

The biosynthesis of herpesvirus DNA in rabbit kidney cells is inhibited to 50% by PEA (2-Phenylethanol) at 0.65 mg PEA/ml. The inhibition of cellular DNA synthesis in uninfected cells by PEA is about twice as sensitive as that of viral DNA synthesis.

Virusvermehrung und Replikation

Als obligate Zellschmarotzer haben Viren keinen eigenen Stoffwechsel. Sie mussen daher fur ihre Vermehrung Zellen infizieren. Die Viruspartikel mussen in der Lage sein, bestimmte Rezeptormolekule auf der Cytoplasmamembran der Wirtszelle zu erkennen und sich an diese anzuheften. Diesen Prozess bezeichnet man als Adsorption. Bei den umhullten Viren wird diese Wechselwirkung durch Proteine vermittelt, welche in die Membranhulle der Virionen eingelagert sind. Das ist unter anderem bei Retro-, Influenza- und Herpesviren der Fall. Die Bindung der viralen Membranproteine an zellulare Oberflachenstrukturen ist zum Teil sehr spezifisch; dies gilt beispielsweise fur die Interaktion zwischen dem Oberf…

Viren mit einzelsträngigem, kontinuierlichem RNA-Genom in Negativstrangorientierung

Die Viren, die ein einzelstrangiges, durchgangiges RNA-Genom in Negativstrangorientierung haben, fasst man in der Ordnung der Mononegavirales zusammen. Zu ihnen zahlen die Familien Rhabdoviridae, Bornaviridae, Paramyxoviridae und Filoviridae.

Localization of latency-associated transcripts in the uterovaginal plexus of herpes simplex virus type 1 and 2 latently infected mice.

The vagina and medulla of the adrenal gland of mice vaginally infected with herpes simplex virus (HSV) types 1 and 2 were examined in the latent stage of infection (5 to 51 weeks post-infection). RNA in situ hybridization with HSV-1 and -2 latency-associated transcript (LAT) RNA probes resulted in positively stained neuronal cell nuclei in the uterovaginal plexus, but not in the medulla of the adrenal gland. These organs were chosen because HSV antigens can be detected not only in the vaginal epithelium, but also in neurons of the uterovaginal plexus and in the medulla of the adrenal gland at the acute stage of genital infection. To our knowledge, this is the first report describing LATs in…

Suppression of humoral immune response against herpes simplex virus induced by defective strains, ts- and TK- mutants.

Suppression of humoral antibody formation against HSV is not only induced by replicating Herpes simplex virus type 2 (HSV-2) but also by the defective strain ANG and the deletion mutant 1301 of Herpes simplex virus type 1 (HSV-1). Moreover, ts-mutants A, H, K, S, 1201 and 1208 of HSV-1 as well as some ts-mutants of HSV-2 and “defective-interfering” particles of HSV-1 after high multiplicity of infection-passages induced suppression. Treatment of infected mice with ACG reduced antibody-formation but did not result in suppression. UV-irradiation of the antibody producing strain Len of HSV-1 strongly reduces antibody formation and induces suppression. Experiments using a series of intertypic r…

Virologie in der Krankenhaushygiene

Die Krankenhaushygiene befast sich mit der Erkennung und Verhutung von nosokomialen Infektionen. Sie betrifft die Ubertragungsmoglichkeiten von Viren im Bereich von arztlichen Einrichtungen von der Arztpraxis bis zum Grosklinikum und bezieht sich dabei auf die Infektionsmoglichkeiten zwischen Patient und arztlichem Personal innerhalb der raumlichen Gegebenheiten.

Suppression of humoral antibody formation against sheep red blood cells by infections with HSV-2 and the influence of mouse cytomegalovirus

HSV-2 infections suppress the antibody response to HSV-1 but do not impair the mouse cytomegalo virus (MCMV) antibody generating system. In contrast, the sheep red blood cell (SRBC) IgM response is impaired by preinfections with HSV-2 but not with HSV-1. From the time kinetics of this suppression it can be concluded that only a certain submechanism "spills over" to the SRBC system. MCMV suppresses the antibody formation induced by HSV-1.

Influence of dibutyryl cyclic AMP on thymidine uptake by herpes simplex virus infected cells and the intracellular level of cyclic AMP.

Abstract Dibutyryl cyclic AMP inhibits the increase of dThd and BrdUrd transport normally observed after infection with Herpesvirus hominis, type I and II. Incorporation is also reduced. Inhibition of uptake is non-competitive as analysed by the Lineweaver-Burk plot. Addition of this drug to infected cells also reduces the activity of the thymidine kinase (EC 2.7.1.75). Transport of dUrd, dCyd and dAdo is not reduced. 4–8 h after infection with thymidine kinase (+) herpes strains the level of cAMP increases. On infection with a thymidine kinase (−) virus, only a small elevation of cAMP can be shown. It was also found that early addition of actinomycin D or of cycloheximide prevents the incr…

Cytokine, Chemokine und Interferone

M. Hoskins sowie George M. Findlay und F. O. MacCallum entdeckten 1935 das Phanomen der Interferenz: Versuchstiere, die mit avirulenten Gelbfieberviren inokuliert wurden, erwiesen sich in den folgenden 24 Stunden vor Infektionen mit dem Wildtypvirus geschutzt. Die Ursache der Interferenz blieb lange Zeit unklar, bis 1957 Alick Isaacs und Jean Lindenmann in infizierten, bebruteten Huhnereiern die Substanz Interferon nachweisen konnten. Anfangs nahm man an, dass der durch Interferon vermittelte Abwehrmechanismus gegen „Fremdnucleinsauren“ gerichtet sei, da sich Interferon durch die doppelstrangige RNA der Reoviren effektiv induzieren lies. Seine Wirkungsweise war jedoch nicht sehr selektiv. E…

Virusbegriff — Struktur — Einteilung

Viren sind vermehrungsfahige Komplexe aus Nukleinsauren mit Proteinen und z. T. Lipiden in definierter Partikelform. Sie vermehren sich nur innerhalb von lebenden Zellen. Sie konnen in die Zelle eindringen und deren Stoffwechselapparat zur eigenen Replikation verwenden. Sie sind in langen Zeitspannen in Wechselwirkung mit ihren Wirten entstanden.

Viren mit doppelsträngigem DNA-Genom

Es sind viele Viren mit einem doppelstrangigen DNAGenom bekannt, die Saugetiere infizieren. Sie werden in sieben Virusfamilien eingeteilt: Hepadnaviridae, Polyomaviridae, Papillomaviridae, Adenoviridae, Herpesviridae, Poxviridae und Asfarviridae. Mit Ausnahme der Pox- und Asfarviridae hat man in allen Familien Vertreter gefunden, die in Menschen oder Tieren persistierende Infektionen herbeifuhren konnen. Hepadna-, Polyoma-,Papilloma- und Herpesviren stehen in enger kausaler Beziehung zu Tumorerkrankungen des Menschen. Dies legt nahe, dass Doppelstrang-DNA-Viren uber vielerlei Moglichkeiten verfugen, die Ablaufe der Zellteilung zu regulieren und zu beeinflussen. Die Hepadnaviren, die zu Begi…

Erkrankungen des Respirationstraktes

Der Schnupfen ist eine sehr haufige, aber harmlose Erkrankung, die eine geringe klinisch-pathologische Bedeutung besitzt; sie ist jedoch von groser wirtschaftlicher Bedeutung: Als Ursache fur Krankmeldungen, fur Ausfall von Unterricht und den Verbrauch groser Mengen an Medikamenten. Der Erreger ist das Common Cold Virus (Schnupfenvirus), das in mehr als 100 Typen vorkommt.

Viren: Definition, Aufbau, Einteilung

Viren sind infektiose Einheiten mit Durchmessern von etwa 16 nm (Circoviren) bis uber 300 nm (Pockenviren; ▸Tabelle 2.1). Ihre geringe Grose macht sie ultrafiltrierbar, das heist, sie werden durch bakteriendichte Filter nicht zuruckgehalten. Viren haben sich wahrend der Evolution in Millionen von Jahren entwickelt und an bestimmte Organismen beziehungsweise deren Zellen angepasst. Die infektiosen Viruspartikel oder Virionen bestehen aus Proteinen und sind bei einigen Virustypen von einer Lipidmembran umgeben, die man oft als Hulle oder Envelope bezeichnet; die Partikel enthalten jeweils nur eine Art von Nucleinsaure, namlich entweder DNA oder RNA. Viren vermehren sich nicht durch Teilung wi…

DNA-replication complex from cells infected with herpes virus.

Herpes simplex virus (HSV) DNA synthesis is initiated in an intact cell system by a 36-residue ribonucleotide stretch [W.E.G. Müller, R.K. Zahn, J. Arendes, and D. Falke (1979) Virology, 98, 200-210]. In the present study a nucleoplasmic fraction was isolated from rabbit kidney cells infected with HSV (type 1), which catalyzes DNA synthesis. By means of specific assays, containing single-stranded deoxyribopolymers, it was elucidated that the replication complex contains both an RNA-synthesizing and a DNA-synthesizing enzyme. These enzymes were characterized as host cell RNA polymerase II and HSV-induced DNA polymerase. The RNA polymerase II synthesizes an RNA initiator with an average chain…

IS LA-PROTEIN INVOLVED IN AUTOIMMUNIZATION AND INFLAMMATORY EVENTS DURING DISEASE - CHARACTERIZATION OF LA-PROTEIN AS AN UNWINDING ENZYME

The effect of Dextransulfate 500 on the pathogenesis of herpes simplex virus infections in weanling mice

Intraperitoneal (i.p.) injection of Dextran Sulfate (D.S.) 500 during a limited period of time influences the course of herpes simplex-virus-infections. D.S.500 was found to reduce the resistance of mice for some herpes simplex-virus strains (Len, L3-2s, Haase) if given between 16 hours before and 2 hours after i.p. infection. The decrease of resistance could be correlated with an increase of the virus content of liver, spleen, brain and spinal cord. Injection of herpes simplex-virus-specific immune serum counteracted the effect of D.S.500 on the course of infections. Conversely, D.S.500 increased the resistance of mice to another group of herpes simplex-viruses (strains D-316, Thea, DD), i…

Viren mit einzelsträngigem DNA-Genom

Bisher sind unter den human- und tierpathogenen Viren nur wenige bekannt, deren Genom als einzelstrangige DNA vorliegt: die Parvoviridae verfugen uber eine lineare, die Circoviridae und die erst kurzlich geschaffene Familie der Anelloviridae uber eine zirkular vorliegende Einzelstrang-DNA. Eine zirkulare, einzelstrangige DNA zeichnet auch die Geminiviridae aus, sie infizieren jedoch ausschlieslich Pflanzen. Circoviren sind virale Pathogene in Pflanzen und verschiedenen Tieren (Affen, Schweinen und Geflugel). 1997 konnte man erstmals ein zirkulares, einzelstrangiges DNA-Virus, das TT-Virus, aus dem Menschen isolieren. Es wird heute zu den Anelloviren gruppiert und persistiert ahnlich wie das…

Correlation of virus replication, cytokine (TNF-? and IL-1) producing cells, neuronal necrosis and inflammation after intranasal infection of mice with herpes simplex virus strains of different virulence

The number of TNF-alpha and IL-1 beta producing cells was investigated during the acute replication phase of herpes simplex virus (HSV) in trigeminal ganglia after intranasal infection with strains of different virulence. The highly virulent strain WAL replicated strongly and induced many cytokine producing cells early in the ganglia. The low virulent strain HFEM replicated less, only few cytokine producing cells were detected late. The thymidine-kinase negative (TK-) virus 1301 did not replicate but produced some lymphocytic inflammation. The higher the virulence of strains of HSV-1 or -2 was, the stronger was the extent of histopathological lesions; moreover, a dissociation in time betwee…

Loss of surface fibronectin after infection of cultured cells by HSV-1 and 2

Fibronectin is lost from the surface of HSV infected cells during cell rounding. In order to investigate also the fate of fibronectin during the process of HSV-induced cell-fusion, BHK, Vero as well as primary or secondary rabbit kidney cells were infected with HSV-1 strains producing cell-fusion. By immunofluorescence and immunoelectron microscopy a considerable loss of fibronectin after HSV infection could be demonstrated leaving only irregular clumps of fibronectin containing virus particles on the cell surface. Decrease and disarrangement of fibronectin was similar during cell rounding and cell fusion. Loss of Fibronectin was closely connected with the two types of the cytopathic effect…

Viren mit einzelsträngigem, segmentierten RNA-Genom in Negativstrangorientierung

Bis heute sind drei Virusfamilien bekannt, deren Vertreter ein RNA-Genom mit negativer Orientierung besitzen, das in den infektiosen Viruspartikeln nicht als ein kontinuierliches Molekul, sondern in mehreren Segmenten vorliegt. Es handelt sich um die Arenaviridae, die Bunyaviridae und die Orthomyxoviridae. Ahnlich wie die Mononegavirales (▸ Kapitel 15) benotigen auch sie fur die Synthese der mRNA und fur die Replikation ein spezielles Enzym, das zusammen mit weiteren Virus-komponenten bei der Infektion in die Zelle gelangt: die RNA-abhangige RNA-Polymerase. Ein in Segmenten vorliegendes Genom ermoglicht den Viren die Bildung von Reassortanten. Hier werden die RNA-Molekule bei Doppelinfektio…

Replication of HSV-1 in murine peritoneal macrophages: comparison of various virus strains with different properties.

The in vitro replication of eleven different strains of herpes simplex virus type 1 was studied in resident or thioglycollate-stimulated mouse macrophages. The strains of herpes simplex virus differed in the type of cytopathic effect, induction capacity for herpes simplex virus coded thymidine kinase and pathogenicity in the mouse. Herpes simplex virus replicated better in thioglycollate-stimulated macrophages than in resident macrophages. In vitro ageing of macrophages increased their replicative potency. Herpes simplex virus replicated better in macrophages from homozygous bg/bg C57/BL6J mice than in macrophages from their heterozygous littermates. Separation of macrophages on discontinuo…

The region 0.7615-0.796 m.u. of the HSV-1 genome determines suppression of humoral antibody formation against herpes simplex virus.

The influence of genetic properties of parts of the HSV-1 genome on suppression of humoral antibody formation was investigated by using intratypic recombinants. The deleted strain HFEM (HSV-1) induces suppression. The MluI DNA fragment (coordinates 0.7615–0.796 m.u.) derived from the antibody inducing strain F1 (HSV-1) was transfected into the deleted strain HFEM to produce the recombinant virus R-MlCI and shown to restore antibody formation, as demonstrated by neutralization- and ELISA-tests. The intratypic recombinant viruses R-15, R-19 and R-26, produced by transfection of the Bam HI DNA-fragment B (0.738–0.809 m.u.) of strain Fl into the deleted strain HFEM, resulted in antibody formati…