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While previous studies have demonstrated that envelope (E) glycoprotein variation between dengue viruses (DENV) genotypes can influence antibody neutralization potency, the mechanisms of variable neutralization remain incompletely understood. Here we characterize epitope antibody interactions of a DENV-3 EDIII binding mouse mAb 8A1 which displays highly variable neutralizing activity against DENV-3...
The human immunodeficiency virus type I (HIV-1) Vpr plays an essential role in viral replication. A number of studies have reported that Vpr modulates the nuclear factor-κB (NF-κB) pathway. Yet, the reported effects of Vpr on NF-κB signaling are controversial. In this study, we investigate the interplay between Vpr and NF-κB pathway. We discover that HIV-1 infection elevates the phosphorylation of...
Hepatitis C virus (HCV) contributes substantially to human morbidity and mortality world-wide. The development of HCV genomes expressing heterologous proteins has enhanced the ability to study viral infection, but existing systems have drawbacks. Recombinant viruses often require adaptive mutations to compensate for reduced viral titers, or rely on an artificial genomic organization that uncouples...
Sylvatic dengue viruses (DENV) are both evolutionarily and ecologically distinct from human DENV and are maintained in an enzootic transmission cycle. Evidence of sylvatic human infections from West Africa and Southeast Asia suggests that sylvatic DENV come into regular contact with humans. Thus, this potential of emergence into the human transmission cycle could limit the potential for eradicating...
Nonspecific anti-inflammatory drugs have been purported to reduce the burden of severe influenza disease. We demonstrate that, unlike oseltamivir administration, simvastatin administration did not reduce morbidity, mortality, or viral load of mice infected with H1N1 or H5N1 viruses. No added benefit to the efficacy of oseltamivir therapy was observed when mice were treated in combination with simvastatin...
Various forms of hepatitis C virus (HCV)-related particles are produced from HCV-infected cells. Measuring infectivity of a HCV sample with the conventional ‘foci counting method’ is laborious and time-consuming. Moreover, the infectivity of a HCV sample does not correlate with the amount of viral RNA that can be measured by real-time RT-PCR. Here we report a new assay suitable for quantifying infectious...
The 5′ untranslated region (UTR) is believed to be vital for the replication of porcine reproductive and respiratory syndrome virus (PRRSV), yet its functional mechanism remains largely unknown. In this study, to define the cis-acting elements for viral replication and infectivity, The 5′ UTR swapping chimeric clones pTLV8 and pSHSP5 were constructed based on two different genotypes full-length infectious...
A functional study of mutants of the human immunodeficiency virus type 1 (HIV-1) integrase (IN) was conducted with the support of a recently proposed HIV-1 intasome model. Firstly, we investigated the predicted position of the C-terminal domain (CTD) and the flexibility of the alpha-6 helix by mutating the residue Ile-203. This had no impact on the 3′-processing reaction but reduced the strand transfer...
HIV-1 Nef is required for efficient viral replication and pathogenesis. However, the extent to which Nef's functions are maintained in natural sequences during chronic infection, and their clinical relevance, remains incompletely characterized. Relative to a control Nef from HIV-1 strain SF2, HLA class I and CD4 down-regulation activities of 46 plasma RNA Nef sequences derived from unique chronic...
One common feature of positive-strand RNA viruses is the association of viral RNA and viral RNA replicase proteins with specific intracellular membranes to form RNA replication complexes. Wuhan nodavirus (WhNV) encodes protein A, which is the sole viral RNA replicase. Here, we showed that WhNV protein A closely associates with mitochondrial outer membranes and colocalizes with viral RNA replication...
The role of IRF7 in the host response to lymphocytic choriomeningitis virus (LCMV) Armstrong 53b infection of mice was investigated. Intracranial infection of IRF7 KO mice was associated with delayed onset of LCM, increased survival and significantly reduced expression of the Ifng gene in the brain but not in the periphery. IRF7 KO mice showed impaired control of LCMV replication and delayed clearance...
Human cytomegalovirus (HCMV) is a member of the Herpesviridae family that manipulates host immune responses and establishes life-long latent infection, in part through mimicry of cytokines, chemokines, and chemokine receptors. The HCMV US27 gene product is a putative chemokine receptor with no known ligands. We generated a stable US27 cell line to screen for chemokine ligands but unexpectedly found...
Identifying host factors provides an important clue to understand virus infection. We selected 10 host factor candidate genes and each gene was silenced in Nicotiana benthamiana (N. benthamiana) to investigate their roles in virus infection. The resulting plants were infected with Tobacco mosaic virus (TMV). The accumulation of viral coat protein and the spread of virus were greatly reduced in the...
Traditional virus inoculation of plants involves mechanical rubbing of leaves, whereas in nature viruses like Tomato bushy stunt virus (TBSV) are often infected via the roots. A method was adapted to compare leaf versus root inoculation of Nicotiana benthamiana and tomato with transcripts of wild-type TBSV (wtTBSV), a capsid (Tcp) replacement construct expressing GFP (T-GFP), or mutants not expressing...
RNAi could protect experimental animals from Foot-and-mouth disease virus (FMDV), but pivotal issue is delivery of RNAi. In this study, shRNA recombinant lentiviral plasmid RNAi-LT6 targeting VP1 of FMDV, which strongly suppressed the transient expression of a FLAG-tagged VP1 protein in 293T cells and significantly inhibited viral replication in BHK-21 cells, was screened and transfected into bovine...
Herpes simplex virus (HSV) has evolved multiple strategies to modulate host immune responses. In a screen of HSV open reading frames to identify additional HSV-encoded proteins that affect NF-κB signaling, we identified the viral U S 3 tegument protein as an inhibitor of NF-κB signaling. We found that the U S 3 protein is required for inhibition of TLR2 signaling induced by viral infection...
The bovine papillomavirus type 1 (BPV1) E2 protein binds as a dimer to the viral genome to promote its transcription, replication and maintenance in keratinocytes. Although BPV1 E2 dimerizes primarily through its DNA-binding domain, it was shown previously that its transactivation domain (TAD) can also dimerize in vitro through formation of a disulfide bond between cysteine 57 (C57) of adjacent monomers...
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