Herpesvirus Regulation of Selective Autophagy

Abstract

Selective autophagy has emerged as a key mechanism of quality and quantity control responsible for the autophagic degradation of specific subcellular organelles and materials. In addition, a specific type of selective autophagy (xenophagy) is also activated as a line of defense against invading intracellular pathogens, such as viruses. However, viruses have evolved strategies to counteract the host's antiviral defense and even to activate some proviral types of selective autophagy, such as mitophagy, for their successful infection and replication. This review discusses the current knowledge on the regulation of selective autophagy by human herpesviruses.

Keywords: aggrephagy; autophagy; ferritinophagy; herpesviruses; mitophagy; nucleophagy; selective autophagy; virophagy.

Figure 1

Overview of the regulation of selective autophagy by herpesviruses. (A) Mitophagy. HHV-8 vIRF-1 activates NIX-mediated mitophagy during lytic replication. (B) Nucleophagy. EBV BFRF1 promotes nuclear vesicle-mediated autophagy following reactivation. (C) Aggrephagy. MCMV M45 promotes the aggregation of RIPK1 and NEMO and then autophagic clearance of the aggregated proteins. (D) Ferritinophagy. HCMV pUL38 inhibits NCOA4-mediated autophagy by interacting with USP24, which destabilizes NCOA4. (E) Virophagy. The Fanconi anemia proteins FANCA and FANCC mediate autophagic clearance of HSV-1. In addition, p62/SQSTM1-mediated virophagy can be activated by TRIM23 or STING via TBK1 after HSV-1 infection. The ICP0 protein downregulates the autophagy receptor p62/SQSTM1 during the early stages of HSV-1 infection, and the Us11 protein excludes TBK1 from the TRIM23/HSP90 complex to inhibit autophagy-mediated restriction of HSV-1 infection. Viral proteins are highlighted within gray capsules.