Orchestrated efforts on host network hijacking: Processes governing virus replication

Dai, Xiaofeng; Hakizimana, Olivier; Zhang, Xuanhao; Kaushik, Aman Chandra; Zhang, Jianying

Mechanisms leading to delayed, weak or no IFN induction are diverse ( Figure 3 ). First, viruses have evolved various strategies to escape innate immune surveillance. For example, HIV-1 modifies PAMPs by altering or hiding its nucleic acids in the viral capsid to mimic the cellular proteins, and randomly mutates its RNA genome to evade host immune recognition [73] ; mononegavirale masks its RNA structure by adding a cap to obviate 3ʹppp end exposure from RLR recognition and/or minimizes the production of transcript agonists of RIG-I [74] ; West Nile virus evades host anti-viral detection via de novo synthesis of 2′-O methylation of the 5ʹ cap of its RNA [75] ; flavivirus achieves this by producing the NS5 proteins that perform 2ʹ-O methylation of internal adenosine of viral RNA in vivo and host ribosomal RNAs in vitro [75] . Second, cellular sensors of immune response such as RIG-I can be targeted by viruses. For instance, HBV produces oncoprotein HBx to prevent the RIG-I induced IFN response and encodes other viral proteins to target adaptor proteins of the RIG-I mediated pathway [76] . Third, viruses inhibit immune response by targeting IFN-regulatory factors such as IRF3. For example, the polymerase of the retrovirus HBV inhibits IRF activation, and rotavirus provides nonstructural protein 1 (NSP1) to degrade IRF3 that induces IFN response on viral infection [60] . Lastly, virus uncoating programs allow capsids to navigate the cell and disassemble in consecutive steps to ensure that genomes are released safely and under precise spatio-temporal control for replication to occur without being detected by the immune system [77] .