Hijacking autophagy for infection by flaviviruses

Abstract

Autophagy is a lysosomal degradative pathway, which regulates the homeostasis of eukaryotic cells. This pathway can degrade misfolded or aggregated proteins, clear damaged organelles, and eliminate intracellular pathogens, including viruses, bacteria, and parasites. But, not all types of viruses are eliminated by autophagy. Flaviviruses (e.g., Yellow fever, Japanese encephalitis, Hepatitis C, Dengue, Zika, and West Nile viruses) are single-stranded and enveloped RNA viruses, and transmitted to humans primarily through the bites of arthropods, leading to severe and widespread illnesses. Like the coronavirus SARS-CoV-II, flaviviruses hijack autophagy for their infection and escape from host immune clearance. Thus, it is possible to control these viral infections by inhibiting autophagy. In this review, we summarize recent research progresses on hijacking of autophagy by flaviviruses and discuss the feasibility of antiviral therapies using autophagy inhibitors.

Keywords: Antiviral therapy; Autophagy; Flavivirus; Hijacking.

Graphical abstract

Fig. 1

Schematic mode of the macroautophagy process. There are different types of autophagy: reticulophagy (for degrading endoplasmic reticulum), mitophagy (mitochondria), ribophagy (ribosomes), and xenophagy (bacteria and viruses). A double-membrane sequestering compartment termed the phagophore matures into an autophagosome.

Fig. 2

Genome structure of flaviviruses. The genome of flaviviruses encodes a long open reading frame flanked by a capped 5-terminus and lacks the poly A tail of the 3-terminus. (A) Under the cooperation of virus and cell protease, the translated single polypeptide is cleaved into three structural proteins, namely capsid protein (C protein), pre-membrane protein (prM protein) and envelope protein (E protein), and seven non-structural (NS) proteins, namely non-structural protein 1 (NS1), NS2A, NS2B, NS3, NS4A, NS4B, and NS5. (B) Hepatitis C virus cleaved into p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B.