Orchestrated efforts on host network hijacking: Processes governing virus replication

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

Early cell apoptosis after virus infection is a catastrophe for viral survival, and viruses have developed various strategies to block early apoptosis for the maintenance of persistent infection ( Figure 2 ) [45] . Some viruses have evolved certain proteins homologous to BCL2 (a crucial anti-apoptotic process) to inhibit host apoptosis, with E1B 19K proteins of adenovirus, BHRF1 of the Epstein-Barr virus (EBV), and HS5A of HCV being typical examples [46] [47] [48] . Some viruses encode viral proteins targeting TP53 given its central roles in growth arrest and apoptosis. While many viral proteins, including adenovirus E1B, the large T antigen of SV40, HBV oncoprotein HBx, IE84 from human CMV, and EBNA5 from EBV, inhibit TP53 activity through direct interactions, E6 of the high-risk human papillomavirus (HPV) serotypes rapidly degrades TP53 via ubiquitin-directed pathway [49, 50] . Some viruses encode proteins inhibiting the interleukin-1 converting enzyme family of cysteine proteases, which are pro-apoptotic. Examples here include crmA of cowpox virus, IAP and TP35 of baculoviruses [51 52,] . Many viruses have evolved multiple ways to suppress host apoptosis. Take the influenza A virus for instance, many of its encoding proteins interfere with apoptosis, including neuraminidase that activates BCL2 and the nonstructural protein 1 (NS1) that stimulates the PI3K/ AKT pathway [53] .