Orchestrated efforts on host network hijacking: Processes governing virus replication

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

Autophagy can be modulated to favor viral replication ( Figure 1 ) [23] . First, viruses can hijack host autophagy pathway to deliver their particles to the replication sites. For instance, rotavirus can hijack the membrane trafficking pathway of autophagy to transport its viral proteins to the site for genome replication and viral assembly [24] , and the same mechanism may also apply to bluetongue virus (BTV) [25] . Second, autophagosomes provide the scaffold and concentrate nutrients for viral replication, and protect the intermediates from immune detection for, mostly, positivestranded RNA viruses. Examples include poliovirus [26] , HIV [27] , dengue virus (DENV) [28] and hepatitis C virus (HCV) [29 30,] . Third, autophagy provides nutrients for viral replication. For example, lipid droplets from the degradation of cholesterol in autolysosomes are required for HCV assembly [31] ; bluetongue viruses induce autophagy to provide a sustainable cellular environment including, e.g. degraded nutrients and acidic condition to avail their replication [32] . Fourth, autophagy machinery facilitates the late stage of viral lifecycle including capsid maturation, envelopment (if applicable), and virus egress. For instance, proper maturation and envelopment of HIV and HBV involves physical interactions between their glycoproteins and autophagy elements such as LC3 [33] ; and autophagosomes help the non-lytic egress of nonenveloped polioviruses through fusing doublemembraned vesicles and plasma membrane [34] . Fifth, viruses such as influenza A modulate autophagy signaling by inhibiting MHC antigen presentation, which can prevent viruses from immune surveillance and create a favorable environment for viruses to survive [35] . Lastly, many viruses such as herpes simplex virus-1 (HSV-1) [36] , cytomegalovirus (CMV) [37] , and Kaposi's sarcoma herpesvirus (KSHV) [38] have developed strategies to suppress autophagy and avoid degradation.