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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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The transactive response DNA-binding protein (TARDBP/TDP-43) is known to stabilize the anti-HIV-1 factor, histone deacetylase 6 (HDAC6). TDP-43 has been reported to determine cell permissivity to HIV-1 fusion and infection acting on tubulin-deacetylase HDAC6. Here, we studied the functional involvement of TDP-43 in the late stages of the HIV-1 viral cycle. The overexpression of TDP-43, in virus-producing cells, stabilized HDAC6 (i.e., mRNA and protein) and triggered the autophagic clearance of HIV-1 Pr55Gag and Vif proteins. These events inhibited viral particle production and impaired virion infectiveness, observing a reduction in the amount of Pr55Gag and Vif proteins incorporated into virions. A nuclear localization signal (NLS)-TDP-43 mutant was not able to control HIV-1 viral production and infection. Likewise, specific TDP-43-knockdown reduced HDAC6 expression (i.e., mRNA and protein) and increased the expression level of HIV-1 Vif and Pr55Gag proteins and α-tubulin acetylation. Thus, TDP-43 silencing favored virion production and enhanced virus infectious capacity, thereby increasing the amount of Vif and Pr55Gag proteins incorporated into virions. Noteworthy, there was a direct relationship between the content of Vif and Pr55Gag proteins in virions and their infection capacity. Therefore, for TDP-43, the TDP-43/HDAC6 axis could be considered a key factor to control HIV-1 viral production and virus infectiveness. [ABSTRACT FROM AUTHOR]

Viruses are key players in the marine ecosystem. It is critical to study specific viral processes and their inter-relationship with various biotic and abiotic variables to quantify their impact on the marine environment. This study investigates the influence of seasonality on viral distribution and their mediated processes in the coastal region of the southeastern Arabian Sea (India) for two consecutive years (2014 and 2015). Water samples were collected from four sampling stations, S1, S2, S3 and S4, in the southeastern Arabian Sea on a monthly basis. Samples were analyzed for the variations in viral abundance, viral production, and viral-induced host mortality covering three seasons namely, pre-monsoon, monsoon and post-monsoon. Viruses and bacteria were enumerated by epifluorescence microscopy following staining with SYBR Green I and viral production was estimated using viral dilution method. Seasonal variations in viral-mediated mortality and microzooplankton grazing mortality of phytoplankton hosts were estimated by modified dilution method. The results revealed a pronounced seasonal pattern of viral abundance (0.04–4.03 × 107 viruses mL−1) and viral production (0.71 × 1010–4.94 × 1010 L−1d−1). The observed high viral-induced mortality of prokaryotes (25.85%) and phytoplankton (7.98–28.9%) during the pre-monsoon season was eventually linked to high viral abundance and production rates. Viral-mediated processes were essentially linked to host density and water temperature. Transmission electron microscopy analysis revealed that myoviruses and non-tailed viruses were dominant in the study region with rod-shaped bacteria being more susceptible to viral infection. The results indicated the prevalence of seasonally induced active viral processes in this tropical marine ecosystem which may significantly contribute to rapid recycling of nutrients in this region. [ABSTRACT FROM AUTHOR]

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]

HIV Nef is a central auxiliary protein in HIV infection and pathogenesis. Our results indicate that HDAC6 promotes the aggresome/autophagic degradation of the viral polyprotein Pr55Gag to inhibit HIV-1 production. Nef counteracts this antiviral activity of HDAC6 by inducing its degradation and subsequently stabilizing Pr55Gag and Vif viral proteins. Nef appears to neutralize HDAC6 by an acidic/endosomal-lysosomal processing and does not need the downregulation function, since data obtained with the non-associated cell-surface Nef-G2A mutant – the cytoplasmic location of HDAC6 – together with studies with chemical inhibitors and other Nef mutants, point to this direction. Hence, the polyproline rich region P72xxP75 (69–77 aa) and the di-Leucin motif in the Nef-ExxxLL160-165 sequence of Nef, appear to be responsible for HDAC6 clearance and, therefore, required for this novel Nef proviral function. Nef and Nef-G2A co-immunoprecipitate with HDAC6, whereas the Nef-PPAA mutant showed a reduced interaction with the anti-HIV-1 enzyme. Thus, the P72xxP75 motif appears to be responsible, directly or indirectly, for the interaction of Nef with HDAC6. Remarkably, by neutralizing HDAC6, Nef assures Pr55Gag location and aggregation at plasma membrane, as observed by TIRFM, promotes viral egress, and enhances the infectivity of viral particles. Consequently, our results suggest that HDAC6 acts as an anti-HIV-1 restriction factor, limiting viral production and infection by targeting Pr55Gag and Vif. This function is counteracted by functional HIV-1 Nef, in order to assure viral production and infection capacities. The interplay between HIV-1 Nef and cellular HDAC6 may determine viral infection and pathogenesis, representing both molecules as key targets to battling HIV. [ABSTRACT FROM AUTHOR]

Efficient inhibition of the HIV infection life cycle at the stages of viral infection, reverse transcription, and post-translational processing has been extensively studied. However, efficient inhibition of HIV assembly and budding has not been reported. Here, we report that dendritic cell-specific intercellular adhesion molecule-3 (ICAM-3) -grabbing nonintegrin (DC-SIGN) and its related protein, DC-SIGNR, effectively block HIV budding from infected cells. Cotransfection of DC-SIGN or DC-SIGNR with HIV demonstrated 95-99.5% inhibition of viral production from host cells. DC-SIGN or DC-SIGNR can also effectively inhibit 90-95% of HIV generation from infected cells. DC-SIGN efficiently reduces the amount of gp120 present on the cell plasma membrane, and completely strips off gp120 from the virions produced by the host cells, suggesting that blockage of HIV budding is due to internalization of gp120 by DC-SIGN. [ABSTRACT FROM AUTHOR]

Papillomavirus L1 and L2, the major and minor capsid proteins, play significant roles in viral assembly, entry, and propagation. In the current study, we investigate the impact of L1 and L2 on viral life cycle and tumor growth with a newly established mouse papillomavirus (MmuPV1) infection model. MmuPV1 L1 knockout, L2 knockout, and L1 plus L2 knockout mutant genomes (designated as L1ATGko-4m, L2ATGko, and L1-L2ATGko respectively) were generated. The mutants were examined for their ability to generate lesions in athymic nude mice. Viral activities were examined by qPCR, immunohistochemistry (IHC), in situ hybridization (ISH), and transmission electron microscopy (TEM) analyses. We demonstrated that viral DNA replication and tumor growth occurred at both cutaneous and mucosal sites infected with each of the mutants. Infections involving L1ATGko-4m, L2ATGko, and L1-L2ATGko mutant genomes generally resulted in smaller tumor sizes compared to infection with the wild type. The L1 protein was absent in L1ATGko-4m and L1-L2ATGko mutant-treated tissues, even though viral transcripts and E4 protein expression were robust. Therefore, L1 is not essential for MmuPV1-induced tumor growth, and this finding parallels our previous observations in the rabbit papillomavirus model. Very few viral particles were detected in L2ATGko mutant-infected tissues. Interestingly, the localization of L1 in lesions induced by L2ATGko was primarily cytoplasmic rather than nuclear. The findings support the hypothesis that the L2 gene influences the expression, location, transport, and assembly of the L1 protein in vivo. [ABSTRACT FROM AUTHOR]