Search results for "Viral replication"

The evolution of collective infectious units in viruses

2019

Viruses frequently spread among cells or hosts in groups, with multiple viral genomes inside the same infectious unit. These collective infectious units can consist of multiple viral genomes inside the same virion, or multiple virions inside a larger structure such as a vesicle. Collective infectious units deliver multiple viral genomes to the same cell simultaneously, which can have important implications for viral pathogenesis, antiviral resistance, and social evolution. However, little is known about why some viruses transmit in collective infectious units, whereas others do not. We used a simple evolutionary approach to model the potential costs and benefits of transmitting in a collect…

The Putative Metal Coordination Motif in the Endonuclease Domain of Human Parvovirus B19 NS1 Is Critical for NS1 Induced S Phase Arrest and DNA Damage

2011

The non-structural proteins (NS) of the parvovirus family are highly conserved multi-functional molecules that have been extensively characterized and shown to be integral to viral replication. Along with NTP-dependent helicase activity, these proteins carry within their sequences domains that allow them to bind DNA and act as nucleases in order to resolve the concatameric intermediates developed during viral replication. The parvovirus B19 NS1 protein contains sequence domains highly similar to those previously implicated in the above-described functions of NS proteins from adeno-associated virus (AAV), minute virus of mice (MVM) and other non-human parvoviruses. Previous studies have show…

ID: 213

2015

The epithelium is the main entry point for many viruses, but the processes that protect barrier surfaces against viral infections are incompletely understood. Here we identified interleukin 22 (IL-22) produced by innate lymphoid cell group 3 (ILC3) as an amplifier of signaling via interferon- λ (IFN- λ ) , a synergism needed to curtail the replication of rotavirus, the leading cause of childhood gastroenteritis. Cooperation between the receptor for IL-22 and the receptor for IFN- λ , both of which were ‘preferentially’ expressed by intestinal epithelial cells (IECs), was required for optimal activation of the transcription factor STAT1 and expression of interferon-stimulated genes (ISGs). T…

Animal models: Murine cytomegalovirus

2002

Publisher Summary This chapter focuses on murine cytomegalovirus (CMV) animal models. Multiple-organ cytomegalovirus disease, interstitial pneumonia in particular, is a major concern in the therapy of hematopoietic malignancies by hematoablative treatment and bone marrow transplantation (BMT). Human CMV (hCMV) is the prototype member of the subfamily, Betaherpesvirinae, of the virus family, Herpesviridae . Its genome is a linear, double-stranded DNA with a coding capacity of ca. 165 open reading frames. During an aeon of co-evolution, CMVs have adapted themselves to their respective hosts; therefore, CMV biology is most reliably studied in a natural virus-host combination. Even though hCMV …

A quantum mechanics/molecular mechanics study of the protein-ligand interaction for inhibitors of HIV-1 integrase.

2007

Human immunodeficiency virus type-1 integrase (HIV-1 IN) is an essential enzyme for effective viral replication. Diketo acids such as L-731,988 and S-1360 are potent and selective inhibitors of HIV-1 IN. In this study, we used molecular dynamics simulations, within the hybrid quantum mechanics/molecular mechanics (QM/MM) approach, to determine the protein-ligand interaction energy between HIV-1 IN and L-731,988 and 10 of its derivatives and analogues. This hybrid methodology has the advantage that it includes quantum effects such as ligand polarisation upon binding, which can be very important when highly polarisable groups are embedded in anisotropic environments, as for example in metal-c…

Bleomycin: Action on growth of oncogenic RNA viruses and on cell transformation

1975

Bleomycin (BLM) inhibits cell proliferation of noninfected chick embryo fibroblasts by blocking their DNA synthesis selectively. Chick embryo fibroblasts have beentransformed by Schmidt-Ruppin D strain of Rous Sarcoma Virus. Transformation has been determined by a focus assay. Foci formation is strongly reduced by BLM. Virus replication is inhibited by BLM in growing and confluent monolayer cells. This result might be explained by the observation that this drug reduces proliferation of growing and of confluent monolayer cells very sensitively. During the first 24 hours after infection the BLM inhibitory effect is more pronounced than in the case of BLM-application during the period 24--48 h…

2018

Tetraspanins (Tspans) are a family of four-span transmembrane proteins, known as plasma membrane “master organizers.” They form Tspan-enriched microdomains (TEMs or TERMs) through lateral association with one another and other membrane proteins. If multiple microdomains associate with each other, larger platforms can form. For infection, viruses interact with multiple cell surface components, including receptors, activating proteases, and signaling molecules. It appears that Tspans, such as CD151, CD82, CD81, CD63, CD9, Tspan9, and Tspan7, coordinate these associations by concentrating the interacting partners into Tspan platforms. In addition to mediating viral attachment and entry, these …

TLR7 controls VSV replication in CD169(+) SCS macrophages and associated viral neuroinvasion

2019

Vesicular stomatitis virus (VSV) is an insect-transmitted rhabdovirus that is neurovirulent in mice. Upon peripheral VSV infection, CD169+ subcapsular sinus (SCS) macrophages capture VSV in the lymph, support viral replication, and prevent CNS neuroinvasion. To date, the precise mechanisms controlling VSV infection in SCS macrophages remain incompletely understood. Here, we show that Toll-like receptor-7 (TLR7), the main sensing receptor for VSV, is central in controlling lymph-borne VSV infection. Following VSV skin infection, TLR7−/− mice display significantly less VSV titers in the draining lymph nodes (dLN) and viral replication is attenuated in SCS macrophages. In contrast to effects o…

Generation of multifunctional murine monoclonal antibodies specifically directed to the VP1unique region protein of human parvovirus B19.

2007

Little is known about the VP1unique region (VP1u), a part of one major capsid protein of human parvovirus B19 (B19), concerning its involvement in viral replication and infection cycle. Showing a phospholipase A2 (PLA2)-like activity, which is discussed to be necessary for viral release from host cell, its precise function remains unclear. The purpose of this study was to generate multifunctional monoclonal antibodies (mabs) for different applications that may be useful in investigating VP1u's relevance. To establish antiVP1u antibodies, spleen cells from Balb/c mice immunized with purified recombinant viral protein were used for generating antibody-producing hybridoma cell lines. Usability…

Treatment of chronic hepatitis C

1991

alpha-Interferon given subcutaneously at doses between 1-3 million units leads to responses in about 50% of patients suffering from chronic hepatitis C. A 24-week treatment is frequently (approx. 50%) followed by relapses reducing the percentage of lasting responders to approx. 20%. The patients who relapse are sensitive to retreatment with interferon-alpha. A better understanding of HCV replication and of the interferon action in this viral disease might help to further improve treatment schedules. Side effects of interferon were frequently mild and readily reversible after cessation of treatment. At present interferon treatment should not be recommended in asymptomatic patients or individ…