STING (stimulator of IFN genes) activates the IFN-dependent innate immune response to infection on sensing the presence of DNA in cytosol. The quantity of STING accumulating in cultured cells varies; it is relatively high in some cell lines [e.g., HEp-2, human embryonic lung fibroblasts (HEL), and HeLa] and low in others (e.g., Vero cells). In a preceding publication we reported that STING was stable in four cell lines infected with herpes simplex virus 1 and that it was actively stabilized in at least two cell lines derived from human cancers. In this report we show that STING is exported from HEp-2 cells to Vero cells along with virions, viral mRNAs, microRNAs, and the exosome marker protein CD9. The virions and exosomes copurified. The quantity of STING and CD9 exported from one cell line to another was inoculum-size-dependent and reflected the levels of STING and CD9 accumulating in the cells in which the virus inoculum was made. The export of STING, an innate immune sensor, and of viral mRNAs whose major role may be in silencing viral genes in latently infected neurons, suggests that the virus has evolved mechanisms that curtail rather than foster the spread of infection under certain conditions. herpes simplex viruses | exosomes | STING | microRNAs | tetraspanins

The research of carbon-based antivirals is still in its infancy, and their development into safe and effective carbon dots (CDs) with antiviral activity at multiple points in the life cycle of the virus remains to be explored. Here, we report a one-step method to apply curcumin in order to prepare of uniform and stable cationic carbon dots (CCM-CDs) with antiviral properties. The inhibitory effect of CCM-CDs on viral replication was studied by using porcine epidemic diarrhea virus (PEDV) as a coronavirus model. PEDV is applied as a coronavirus model to study the antiviral effect of as-prepared CCM-CDs on its replication. The cationic CCM-CDs treatment is found obviously to inhibit the proliferation of PEDV compared with the common CDs (EDA-CDs). The CCM-CDs treatment can change the structure of surface protein in viruses, thereby inhibiting viral entry. It can also suppresses the synthesis of negative-strand RNA of the virus, the budding of the virus, and the accumulation of reactive oxygen species by PEDV. Furthermore, CCM-CDs treatment is also found to suppress viral replication by stimulating the production of interferon-stimulating genes (ISGs) and proinflammatory cytokines. These results offer theoretical support for the development of CCM-CDs as a hopeful antiviral drug for the treatment of coronavirus infections, including PEDV.

Development of novel antiviral reagents is of great importance for the control of virus spread. Here, AgS nanoclusters (NCs) were proved for the first time to possess highly efficient antiviral activity by using porcine epidemic diarrhea virus (PEDV) as a model of coronavirus. Analyses of virus titers showed that AgS NCs significantly suppressed the infection of PEDV by about 3 orders of magnitude at the noncytotoxic concentration at 12 h postinfection, which was further confirmed by the expression of viral proteins. Mechanism investigations indicated that AgS NCs treatment inhibits the synthesis of viral negative-strand RNA and viral budding. AgS NCs treatment was also found to positively regulate the generation of IFN-stimulating genes (ISGs) and the expression of proinflammation cytokines, which might prevent PEDV infection. This study suggest the novel underlying of AgS NCs as a promising therapeutic drug for coronavirus.

In cell cultures, HSV-1 replication is initiated by recruitment by virion protein 16 of transcriptional factors and histone-modifying enzymes to immediate early (α) gene promoters. HSV establishes latent infections characterized by suppression of viral gene expression except for latency-associated transcripts (LATs) and miRNAs. The latent virus reactivates in stressed neurons. A fundamental question is how reactivation initiates in the absence of virion protein 16. We report the following findings in the ganglion explant model. (i) Anti-nerve growth factor antibody accelerated the reactivation of latent virus. Viral mRNAs were detected as early as 9 h after explantation. (ii) After explantation the amounts of viral mRNAs increased whereas amounts of miRNAs and LATs decreased. The decrease in miRNAs and LATs required ongoing protein synthesis, raising the possibility that LAT and miRNAs were degraded by a viral gene product. (iii) The expression of viral genes in explanted ganglia was disordered rather than sequentially ordered as in infected cells in culture. These findings suggest that in reactivating ganglia gene expression is totally derepressed and challenge the current models in that establishment of or exit from latency could not be dependent on the suppression or activation of single or small clusters of viral genes. Finally, miRNAs and LATs reached peak levels 9-11 d after corneal inoculation, thus approximating the pattern of virus replication in these ganglia. These findings suggest that the patterns of accumulation of LATs and miRNAs reflect many different stages in the infection of neurons.T o initiate infection in cell culture and presumably also at the portal of entry into the body, the HSV-1 capsid delivers the DNA to the nucleus. Concurrently, virion protein 16 (VP16), a key viral protein packaged in the virion and delivered to the nucleus, recruits the cellular factors octamer-binding protein 1 (Oct1), host cell factor 1 (HCF1), lysine-specific demethylase 1 (LSD1), circadian locomotor output cycles kaput (CLOCK) histone acetyl transferase, and other transcriptional factors to initiate a cascade of viral gene expression that begins with immediate early (α) genes followed by early (β) and late (γ) genes (1-5). VP16 is encoded by a γ gene expressed late in infection (1). In all, the transcriptional program yields almost 100 different transcripts. In contrast, in latently infected neurons viral gene expression is limited to the latency-associated transcript (LAT) and approximately six or more miRNAs (6, 7). Given the requirement for VP16 to initiate viral replication in productively infected cells, the question arises as to how virus replication initiates in stressed neurons harboring latent virus. Among the many hypotheses, two stand out: That VP16 is expressed first or that in neurons α gene expression can ensue in the absence of VP16.Resolution of this problem requires analyses of the reactivation in ganglia under conditions that are physiologically similar to those that occur in vivo. In the st...

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