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The Zika virus (ZIKV) is a mosquito-borne flavivirus that has reemerged as a serious public health problem around the world. Syndromes of infected people range from asymptomatic infections to severe neurological disorders, such as Guillain-Barré syndrome and microcephaly. Screening anti-ZIKV drugs derived from Chinese medicinal herbs is one method of identifying antiviral agents. In this paper, we report that (1) Cephalotaxine (CET), an alkaloid isolated from Cephalotaxus drupacea , was effective in inhibiting ZIKV activity in vitro (i.e., in Vero and A549 cell lines) and (2) the mechanisms which underlie these effects involve virucidal activity and a decrease in viral replication. Specifically, CET was found to decrease ZIKV RNA and viral protein expression, inhibit ZIKV replication, and inhibit ZIKV mRNA/protein production. We also determined that CET is effective in inhibiting dengue virus 1–4 (DENV1-4). Taken together, our findings indicate that CET could be an effective lead compound in the treatment of ZIKV and also suggest that further investigation and development of CET-derived drugs may lead to a new class of anti- Flavivirus medications. • CET against ZIKV infection via inhibiting replication and stability. • CET was identified as a potent inhibitor of ZIKV infection. • CET as a candidate compound for potential ZIKV treatment. [ABSTRACT FROM AUTHOR]

Understanding the mechanism of HIV-1 latency is crucial to the viral reservoir eradication. Human cellular miRNAs can modulate HIV-1 expression by targeting of viral RNAs or host gene transcripts. To identify miRNAs modulating HIV-1 latency, we determined the miRNA expression profiles of HIV-1 latently infected and productively infected cells by microarray and qRT-PCR. Among the differentially expressed miRNAs, miR-196b and miR-1290 targeted the 3′ untranslated region of HIV-1 and affected its expression. Ectopic expression of these two miRNAs efficiently suppressed HIV-1 production and infectivity. Specific inhibitors of these miRNAs substantially counteracted their effects on HIV-1, as measured either as viral production and infectivity in HEK-293T cells or as HIV-1 RNA expression or viral production in cells isolated from HIV-1-infected individuals. Our study emphasizes the role of cellular miRNAs in HIV-1 latency regulation, and it suggests that inhibitors of miR-196b and miR-1290 could be used to activate latent HIV-1. [ABSTRACT FROM AUTHOR]

Abstract: Rotavirus (RV) infection causes serious dehydrating diarrhoea in infants and newborn animals. Our previous study revealed that cyclophilin A (CYPA), a peptidyl-prolyl cis–trans isomerase (PPIase), could be temporarily upregulated in RV-infected MA104 cells in early stage of infection (unpublished data). To find out the possible roles of CYPA in RV infection, we overexpressed and silenced CYPA in various cell lines by gene transfection and shRNA. We found that transfection of CYPA significantly inhibited RV replication, while silencing the expression of CYPA significantly increased RV replication. Accordingly, overexpression of CYPA significantly increased IFN-β production; while silencing CYPA significantly reduced IFN-β production. This effect of CYPA on IFN-β production was independent of its PPIase activity. Moreover, IFN-β secreted by host cells in RV infection had a critical repressive effect on viral replication. Finally, we found that inhibiting JNK pathway by SP600125 and JNK siRNA abrogated the effect of CYPA on IFN-β transcription in RV-infected MA104 cells. Together, our data suggested that CYPA inhibited RV replication by facilitating host IFN-β production, which was independent on the PPIase activity of CYPA but dependent on the activation of JNK signaling pathway. [Copyright &y& Elsevier]

The cellular prion protein (PrPc) is highly conserved in mammals and expressed widely in different tissues but its physiological role remains elusive. Recently, the human PrPc was shown to possess nucleic acid binding and chaperoning properties similar to human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein, a key viral factor in virus structure and replication. These findings prompted us to determine if PrPc could influence HIV-1 replication. We used the human 293T cell line as a model system, since only a very low level of PrPc accumulates in these cells. Expression of PrP at a high level resulted in a specific decrease of HIV-1 Env and Vpr expression. Despite similar levels of intracellular Gag, virus production was reduced by eightfold and infectivity by three- to fourfold in the presence of PrPc. A PrPc mutant lacking the glycosylphosphatidylinositol (GPI) anchor peptide did not impair HIV-1 production, suggesting that PrPc trafficking is critical for this inhibitory effect. Coexpressing HIV-1 and PrPc in these cells also caused a fraction of PrPc to become partially proteinase K-resistant (PrPres), further illustrating the interactions between HIV-1 and PrPc. [Copyright &y& Elsevier]

• We present a novel ODE model of RSV that includes the effect of syncytia. • Effect of syncytia occurs when R0 from syncytia equals R0 from cell-free transmission. • High fusion rate & low viral production in syncytia leads to slow-growing infections. Respiratory syncytial virus (RSV) is a common, contagious infection of the lungs and the respiratory tract. RSV is characterized by syncytia, which are multinuclear cells created by cells that have fused together. We use a mathematical model to study how different assumptions about the viral production and lifespan of syncytia change the resulting infection time course. We find that the effect of syncytia on viral titer is only apparent when the basic reproduction number for infection via syncytia formation is similar to the reproduction number for cell free viral transmission. When syncytia fusion rate is high, we find the presence of syncytia can lead to slowly growing infections if viral production is suppressed in syncytia. Our model provides insight into how the presence of syncytia can affect the time course of a viral infection. [ABSTRACT FROM AUTHOR]