ImportanceBiological secretions allow viruses to spread between individuals. Each type of secretion has a unique composition of proteins, salts and sugars, which can affect infectivity potential of the virus and inhibition of this process. Here we describe HIV-1 infection and inhibition in whole human semen and a synthetic simulant we formulated. We discovered that the sugar fructose in semen decreases the activity of a broad and potent class of antiviral agents that target mannose sugars on the envelope protein of HIV-1. This effect of semen fructose likely reduces the efficacy of such inhibitors to prevent sexual transmission of HIV-1. Our findings suggest that preclinical evaluation of microbicides and vaccine-elicited antibodies will be improved by in vitro assessment in synthetic formulations, which accurately simulate the effects of semen on HIV-1 infection and inhibition. Copyright © 2020 American Society for Microbiology.Micro (mi)RNAs are small regulatory RNAs, which act by modulating the expression of target genes. In addition to their role in maintaining essential physiological functions in the cell, miRNAs can also regulate viral infections. They can do so directly by targeting RNAs of viral origin or indirectly by targeting host mRNAs and this can result in a positive or negative outcome for the virus. Here, we performed a fluorescence-based miRNA genome-wide screen in order to identify cellular miRNAs involved in the regulation of arbovirus infection in human cells. We identified sixteen miRNAs showing a positive effect on Sindbis virus (SINV) expressing GFP, among which a number of neuron-specific ones such as miR-124. We confirmed that overexpression of miR-124 increases both SINV structural protein translation and viral production and that this effect is mediated by its seed sequence. We further demonstrated that the SINV genome possesses a binding site for miR-124.  https://www.selleckchem.com/products/mlt-748.html  Both inhibition of miR-124 or silent mutations to da genome-wide miRNA screen, we identified the neuronal miR-124 as a positive regulator of the Sindbis and chikungunya alphaviruses. We also showed that this effect was in part direct, thereby opening novel avenues to treat alphaviruses infection. Copyright © 2020 American Society for Microbiology.Vector transmission plays a primary role in the life cycle of viruses and insects are the most common vectors. An important mode of vector transmission, reported only for plant viruses, is the circulative non-propagative transmission where the virus cycles within the body of its insect vector, from gut to salivary glands and saliva, without replicating. This mode of transmission has been extensively studied in the viral families Luteoviridae and Geminiviridae and is also reported for Nanoviridae The biology of viruses within these three families is different and whether they have evolved similar molecular/cellular virus-vector interactions is unclear. In particular, nanoviruses have a multipartite genome organization and how the distinct genome segments encapsidated individually transit through the insect body is unknown. Here, using a combination of fluorescent in situ hybridization and immuno-fluorescence, we monitor distinct proteins and genome segments of the nanovirus Faba bean necrotic stunt virus (FBNScellular mechanisms of the virus-vector interaction are missing. This is striking for nanoviruses that are believed to interact with aphid vectors in ways similar to luteoviruses or geminiviruses but for which empirical evidence is scarce. We here confirm that nanoviruses follow a within-vector route similar to gemini- but distinct from luteoviruses. We show that they produce a non-structural protein mandatory for viral entry into gut cells, a unique phenomenon for this mode of transmission. Finally, nanoviruses being multipartite viruses, we demonstrate that a large amount of viral particles penetrate susceptible cells of the vector, allowing distinct genome segments to remain together. Copyright © 2020 American Society for Microbiology.Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes explosive epidemics of a febrile illness characterized by debilitating arthralgia and arthritis and can endure for months to years following infection. In mouse models, CHIKV persists in joint tissues for weeks to months and is associated with chronic synovitis. Using a recombinant CHIKV strain encoding a CD8+ T cell receptor epitope from ovalbumin, as well as a viral peptide-specific MHC class I tetramer, we interrogated CD8+ T cell responses during CHIKV infection. Epitope-specific CD8+ T cells, which were reduced in Batf3 -/- and Wdfy4 -/- mice with known defects in antigen cross-presentation, accumulated in joint tissue and the spleen. Antigen-specific ex vivo restimulation assays and in vivo killing assays demonstrated that CD8+ T cells produce cytokine and have cytolytic activity. Despite the induction of a virus-specific CD8+ T cell response, CHIKV burden in joint-associated tissues and the spleen were equivalent in wild-type (Win a persistent infection may lead to the development of new therapeutic strategies against chronic CHIKV disease. In this study, we find that CHIKV establishes and maintains a persistent infection in joint-associated tissue in part, by evading antiviral CD8+ T cell immunity. Thus, immunomodulatory therapies that improve CD8+ T cell immune surveillance and clearance of CHIKV infection could be a strategy for mitigating chronic CHIKV disease. Copyright © 2020 American Society for Microbiology.Flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), rely heavily on the availability of endoplasmic reticulum (ER) membranes throughout their lifecycle and degradation of ER membranes restricts flavivirus replication. Accordingly, DENV and ZIKV restrict ER turnover by protease-mediated cleavage of reticulophagy regulator 1 (RETREG1), also known as FAM134B, an autophagy receptor responsible for targeted ER sheet degradation. Given that the induction of autophagy may play an important role in flavivirus replication, the antiviral role of RETREG1 suggests specialized autophagic pathways may have differential effects on the flavivirus lifecycle. We previously identified BPI Fold Containing Family B Member 3 (BPIFB3) as a regulator of autophagy that negatively controls enterovirus replication. Here, we show that in contrast to enteroviruses, BPIFB3 functions as a positive regulator of DENV and ZIKV infection and that its RNAi-mediated silencing inhibits the formation of viral replication organelles.