Search results for "Viral replication"

Relationship between within-host fitness and virulence in the vesicular stomatitis virus: correlation with partial decoupling.

2012

ABSTRACT Given the parasitic nature of viruses, it is sometimes assumed that rates of viral replication and dissemination within hosts (within-host fitness) correlate with virulence. However, there is currently little empirical evidence supporting this principle. To test this, we quantified the fitness and virulence of 21 single- or double-nucleotide mutants of the vesicular stomatitis virus in baby hamster kidney cells (BHK-21). We found that, overall, these two traits correlated positively, but significant outliers were identified. Particularly, a single mutation in the conserved C terminus of the N nucleocapsid (U1323A) had a strongly deleterious fitness effect but did not alter or even …

Murine model of interstitial cytomegalovirus pneumonia in syngeneic bone marrow transplantation: persistence of protective pulmonary CD8-T-cell infil…

2000

ABSTRACTInterstitial pneumonia (IP) is a severe organ manifestation of cytomegalovirus (CMV) disease in the immunocompromised host, in particular in recipients of bone marrow transplantation (BMT). Diagnostic criteria for the definition of CMV-IP include clinical evidence of pneumonia together with CMV detected in bronchoalveolar lavage or lung biopsy. We have used the model of syngeneic BMT and simultaneous infection of BALB/c mice with murine CMV for studying the pathogenesis of CMV-IP by controlled longitudinal analysis. A disseminated cytopathic infection of the lungs with fatal outcome was observed only when reconstituting CD8 T cells were depleted. Neither CD8 nor CD4 T cells mediated…

Persistent and Transient Replication of Full-Length Hepatitis C Virus Genomes in Cell Culture

2002

ABSTRACT The recently developed subgenomic hepatitis C virus (HCV) replicons were limited by the fact that the sequence encoding the structural proteins was missing. Therefore, important information about a possible influence of these proteins on replication and pathogenesis and about the mechanism of virus formation could not be obtained. Taking advantage of three cell culture-adaptive mutations that enhance RNA replication synergistically, we generated selectable full-length HCV genomes that amplify to high levels in the human hepatoma cell line Huh-7 and can be stably propagated for more than 6 months. The structural proteins are efficiently expressed, with the viral glycoproteins E1 and…

Cooperative nature of viral replication

2020

The ability of viruses to infect their hosts depends on rapid dissemination following transmission. The notion that viral particles function as independent propagules has been challenged by recent observations suggesting that viral aggregates show enhanced infectivity and faster spread. However, these observations remain poorly understood. Here, we show that viral replication is a cooperative process, such that entry of multiple viral genome copies into the same cell disproportionately increases short-term viral progeny production. This cooperativity arises from the positive feedback established between replication templates and virus-encoded products involved in replication and should be a…

IN SITU HYBRIDIZATION FOR DETECTION OF HEPATITIS B VIRUS GENOMES IN LIVER TISSUE OF CHRONIC INFECTED CHILDREN

1990

Detection of hepatitis B virus (HBV)-DNA in the liver of chronic infected patients is presently the most sensitive marker of viral replication and infectivity. In situ hybridization (ISH) allows the direct visualization of HBV infected liver cells and distribution of the viral sequences. This study was done to establish ISH and correlate the findings with conventional markers for HBV infection. Methods. Liver biopsies of 50 patients (28 ♂, 22 ♀) aged 0.5-20 years (mean 10.3) with various histological diagnoses were tested by 1SH. The HBV-DNA probe was labeled by nick translation with 35S-CTP to a specific activity of 3-5×108 cpm/μg DNA. Results. HBV-DNA/mRNA could be demonstrated in 38 pati…

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

1993

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…

The herpesviral antagonist m152 reveals differential activation of STING ‐dependent IRF and NF ‐κB signaling and STING 's dual role during MCMV infec…

2019

Cytomegaloviruses (CMVs) are master manipulators of the host immune response. Here, we reveal that the murine CMV (MCMV) protein m152 specifically targets the type I interferon (IFN) response by binding to stimulator of interferon genes (STING), thereby delaying its trafficking to the Golgi compartment from where STING initiates type I IFN signaling. Infection with an MCMV lacking m152 induced elevated type I IFN responses and this leads to reduced viral transcript levels both in vitro and in vivo This effect is ameliorated in the absence of STING Interestingly, while m152 inhibits STING-mediated IRF signaling, it did not affect STING-mediated NF-κB signaling. Analysis of how m152 targets S…

Internalization of Echovirus 1 in Caveolae

2002

ABSTRACT Echovirus 1 (EV1) is a human pathogen which belongs to the Picornaviridae family of RNA viruses. We have analyzed the early events of infection after EV1 binding to its receptor α2β1 integrin and elucidated the route by which EV1 gains access to the host cell. EV1 binding onto the cell surface and subsequent entry resulted in conformational changes of the viral capsid as demonstrated by sucrose gradient sedimentation analysis. After 15 min to 2 h postinfection (p.i.) EV1 capsid proteins were seen in vesicular structures that were negative for markers of the clathrin-dependent endocytic pathway. In contrast, immunofluorescence confocal microscopy showed that EV1, α2β1 integrin, and …

CHARACTERIZATION OF CHRONIC HEPATITIS B IN CHILDHOOD USING MOLECULAR BIOLOGY TECHNIQUES

1992

The introduction of molecular biology techniques in the diagnostics of chronic hepatitis B virus infection proved HBV DNA to be the most sensitive marker of viral replication and infectivity. The aim of our study was to characterize the HBV DNA status in children with chronic hepatitis B with various molecular biology techniques in relation to conventional HBV markers. Methods: 206 sera of 172 and liver tissue of 108 children with chronic hepatitis B infection were investigated by dot blot-, Southern blot-, and in situ hybridization. In dot blot and Southern blot negative specimens polymerase chain reaction (PCR) was performed. Results: 111 of the 206 sera were positive for HBV DNA by dot b…

2014

The lungs are a noted predilection site of acute, latent, and reactivated cytomegalovirus (CMV) infections. Interstitial pneumonia is the most dreaded manifestation of CMV disease in the immunocompromised host, whereas in the immunocompetent host lung-infiltrating CD8 T cells confine the infection in nodular inflammatory foci and prevent viral pathology. By using murine CMV infection as a model, we provide evidence for a critical role of mast cells (MC) in the recruitment of protective CD8 T cells to the lungs. Systemic infection triggered degranulation selectively in infected MC. The viral activation of MC was associated with a wave of CC chemokine ligand 5 (CCL5) in the serum of C57BL/6 m…