Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.

Cell culture system that mimicks complete HBV life cycle from entry to egress.Efficient in vitro infection with crude HBV patient sera.Up to 50-and 1,300-fold net amplification of patient-and cell culture-derived input HBV in the supernatant.Polyethylene glycol-independent HBV spread to adjacent cells, forming infected cell clusters.Evaluation of patient-and cell culture-derived HBV amplification w/wo antivirals over 8 weeks.

Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.

Hepatitis C virus (HCV) is highly dependent on host proteins for its own propagation. By transcriptome sequencing (RNA-Seq) analysis, we identified 30 host genes that were significantly differentially expressed in cell culture-grown HCV (HCVcc)-infected cells. Of these candidate genes, we selected and characterized ankyrin repeat domain 1 (ANKRD1). Here, we showed that protein expression of ANKRD1 was up-regulated in HCVcc-infected cells. We further showed that protein expression level of ANKRD1 was increased by nonstructural 5A (NS5A) protein. ANKRD1 specifically interacted with NS5A both in vitro and coimmunoprecipitation assays. Protein interaction was mediated through the domain II of NS5A and the C-terminal region of ANKRD1. Promoter activity of ANKRD1 was also increased by NS5A protein. Moreover, up-regulation of ANKRD1 expression was mediated through alteration in intracellular calcium homeostasis and ER stress in HCVcc-infected cells. We showed that silencing of ANKRD1 impaired HCV propagation without affecting HCV replication. By using HCV-like infectious particle (HCV-LP), we demonstrated that HCV single-cycle infection was drastically impaired in ANKRD1 knockdown cells. Finally, we verified that ANKRD1 was required for HCV entry. These data suggest that HCV coopts ANKRD1 for its own propagation and up-regulation of ANKRD1 may contribute to HCV-mediated liver pathogenesis.

Background: RAS GTPase-activating proteinbinding protein ( G3BP1) is an RNA-binding protein that is essential for assembling stress granules. Many functions related to the survival and progression of cancer have been reported. The current study aimed to investigate the role of G3BP1 in radio-sensitisation of cancer cells. Materials and Methods: Radiation sensitivity and chemosensitivity were analysed in A549 and H460 cells transfected with G3BP1 siRNAs, and N-acetyl-L-cysteine (NAC) was used to elucidate the involvement of reactive oxygen species (ROS). Results: G3BP1 depletion sensitised lung cancer cell lines to radiation, and the effect was related to ROS. G3BP1 depletion impaired the intracellular ROS scavenging system and NAC abolished the radiation-sensitive phenotypes caused by G3BP1 depletion. Conclusion: The study suggested G3BP1 as a promising target for radio-and chemosensitisation of lung cancer.