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Rab33B and its autophagic Atg5/12/16L1 effector assist in hepatitis B virus naked capsid formation and release
2015
Hepatitis B virus morphogenesis is accompanied by the production and release of non-enveloped capsids/nucleocapsids. Capsid particles are formed inside the cell cytosol by multimerization of core protein subunits and ultimately exported in an uncommon coatless state. Here, we investigated potential roles of Rab GTPases in capsid formation and trafficking by using RNA interference and overexpression studies. Naked capsid release does not require functions of the endosome-associated Rab5, Rab7 and Rab27 proteins, but depends on functional Rab33B, a GTPase participating in autophagosome formation via interaction with the Atg5-Atg12/Atg16L1 complex. During capsid formation, Rab33B acts in conju…
The interplay between the host microbiome and pathogenic viral infections
2021
The microorganisms associated with an organism, the microbiome, have a strong and wide impact in their host biology. In particular, the microbiome modulates both the host defense responses and immunity, thus influencing the fate of infections by pathogens. Indeed, this immune modulation and/or interaction with pathogenic viruses can be essential to define the outcome of viral infections. Understanding the interplay between the microbiome and pathogenic viruses opens future venues to fight viral infections and enhance the efficacy of antiviral therapies. An increasing number of researchers are focusing on microbiome-virus interactions, studying diverse combinations of microbial communities, …
CVB3 VP1 interacts with MAT1 to inhibit cell proliferation by interfering with Cdk-activating kinase complex activity in CVB3-induced acute pancreati…
2021
Coxsackievirus B3 (CVB3) belongs to the genus Enterovirus of the family Picornaviridae and can cause acute acinar pancreatitis in adults. However, the molecular mechanisms of pathogenesis underlying CVB3-induced acute pancreatitis have remained unclear. In this study, we discovered that CVB3 capsid protein VP1 inhibited pancreatic cell proliferation and exerted strong cytopathic effects on HPAC cells. Through yeast two-hybrid, co-immunoprecipitation, and confocal microscopy, we show that Menage a trois 1 (MAT1), a subunit of the Cdk-Activating Kinase (CAK) complex involved in cell proliferation and transcription, is a novel interaction protein with CVB3 VP1. Moreover, CVB3 VP1 inhibited MAT…
Mouse models of cytomegalovirus latency: overview.
2002
Abstract Background: The molecular regulation of viral latency and reactivation is a central unsolved issue in the understanding of cytomegalovirus (CMV) biology. Like human CMV (hCMV), murine CMV (mCMV) can establish a latent infection in cells of the myeloid lineage. Since mCMV genome remains present in various organs after its clearance from hematopoietic cells first in bone marrow and much later in blood, there must exist one or more widely distributed cell type(s) representing the cellular site(s) of enduring mCMV latency in host tissues. Endothelial cells and histiocytes are candidates, but the question is not yet settled. Another long debated problem appears to be solved: mCMV establ…
Internalization of novel non-viral vector TAT-streptavidin into human cells
2007
BMC Biotechnology, 7 (1)
The endogenous retroviral insertion in the human complement C4 gene modulates the expression of homologous genes by antisense inhibition
2001
Intron 9 contains the complete endogenous retrovirus HERV-K(C4) as a 6.4-kb insertion in 60% of human C4 genes. The retroviral insertion is in reverse orientation to the C4 coding sequence. Therefore, expression of C4 could lead to the transcription of an antisense RNA, which might protect against exogenous retroviral infections. To test this hypothesis, open reading frames from the HERV sequence were subcloned in sense orientiation into a vector allowing expression of a beta-galactosidase fusion protein. Mouse L cells which had been stably transfected with either the human C4A or C4B gene both carrying the HERV insertion (LC4 cells), and L(Tk-) cells without the C4 gene were transiently tr…
Infection-induced chromatin modifications facilitate translocation of herpes simplex virus capsids to the inner nuclear membrane
2021
Herpes simplex virus capsids are assembled and packaged in the nucleus and move by diffusion through the nucleoplasm to the nuclear envelope for egress. Analyzing their motion provides conclusions not only on capsid transport but also on the properties of the nuclear environment during infection. We utilized live-cell imaging and single-particle tracking to characterize capsid motion relative to the host chromatin. The data indicate that as the chromatin was marginalized toward the nuclear envelope it presented a restrictive barrier to the capsids. However, later in infection this barrier became more permissive and the probability of capsids to enter the chromatin increased. Thus, although …
The Nasal Epithelium as a Factory for Systemic Protein Delivery
2002
We have previously shown that recombinant Sendai virus (SeV) produces efficient in vivo airway epithelial gene transfer. The ability to produce therapeutic levels of circulating proteins following noninvasive gene transfer would have widespread clinical application. Here, we compared nose, lung, and skeletal muscle for the ability to produce circulating levels of the secreted mouse antiinflammatory cytokine interleukin-10 (IL10) following SeV-mediated gene transfer. High levels of serum IL10 were obtained from each site with a potency order of lung > nose > muscle for a given viral titer. Serum levels from each site were within the likely required range for anti-inflammatory effects. The co…
Modulation of Hepatitis C Virus NS5A Hyperphosphorylation by Nonstructural Proteins NS3, NS4A, and NS4B
1999
NS5A of the hepatitis C virus (HCV) is a highly phosphorylated protein involved in resistance against interferon and required most likely for replication of the viral genome. Phosphorylation of this protein is mediated by a cellular kinase(s) generating multiple proteins with different electrophoretic mobilities. In the case of the genotype 1b isolate HCV-J, in addition to the basal phosphorylated NS5A (designated pp56), a hyperphosphorylated form (pp58) was found on coexpression of NS4A (T. Kaneko, Y. Tanji, S. Satoh, M. Hijikata, S. Asabe, K. Kimura, and K. Shimotohno, Biochem. Biophys. Res. Commun. 205:320‐326, 1994). Using a comparative analysis of two full-length genomes of genotype 1b…
Functional properties of a monoclonal antibody inhibiting the hepatitis C virus RNA-dependent RNA polymerase.
2001
The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp), represented by nonstructural protein 5B (NS5B), has recently emerged as a promising target for antiviral intervention. Here, we describe the isolation, functional characterization, and molecular cloning of a monoclonal antibody (mAb) inhibiting the HCV RdRp. This mAb, designated 5B-12B7, binds with high affinity to a conformational epitope in the palm subdomain of the HCV RdRp and recognizes native NS5B expressed in the context of the entire HCV polyprotein or subgenomic replicons. Complete inhibition of RdRp activity in vitro was observed at equimolar concentrations of NS5B and mAb 5B-12B7, whereas RdRp activities of classica…