The Interplay between Autophagy and Virus Pathogenesis—The Significance of Autophagy in Viral Hepatitis and Viral Hemorrhagic Fevers

Abstract

Autophagy is a process focused on maintaining the homeostasis of organisms; nevertheless, the role of this process has also been widely documented in viral infections. Thus, xenophagy is a selective form of autophagy targeting viruses. However, the relation between autophagy and viruses is ambiguous—this process may be used as a strategy to fight with a virus, but is also in favor of the virus’s replication. In this paper, we have gathered data on autophagy in viral hepatitis and viral hemorrhagic fevers and the relations impacting its viral pathogenesis. Thus, autophagy is a potential therapeutic target, but research is needed to fully understand the mechanisms by which the virus interacts with the autophagic machinery. These studies must be performed in specific research models other than the natural host for many reasons. In this paper, we also indicate Lagovirus europaeus virus as a potentially good research model for acute liver failure and viral hemorrhagic disease.

Factors affecting RIG-I-Like receptors activation - New research direction for viral hemorrhagic fevers

“…As we described earlier, this process affects RLR-dependent inhibition of IFN production. In addition, Beclin-1 knockdown inhibits HTNV replication ( 76 , 97 ), so we speculate that this phenomenon may also be related to the RIG-I-like receptor signaling pathway and interferon production. In Rift Valley Fever Virus (RVFV) infection, silencing of autophagy proteins (Atg5, Atg7 and Becn1) has been shown to negatively affect the host antiviral response and increase viral replication ( 98 ).…”

“…The S segment also encodes a nucleoprotein (NP), which is the major structural component of the nucleocapsid and is the most abundant protein during infection. The L segment encodes the RNA-dependent RNA polymerase L protein and a small, zinc finger protein (Z), which is responsible for virus particle formation ( 76 , 77 ). All human pathogens in the family Arenaviridae belong to the genus Mammarenavirus , which we can further divide into two groups based on geography and phylogeny: Old World (OW) arenaviruses and New World (NW) arenaviruses ( 78 , 79 ).…”

“…Bunyaviruses are a family of spherical, enveloped viruses. They contain three segments of antisense (and sometimes ambisense) single-stranded RNA linked to a nucleoprotein ( 76 ). The two outer glycoproteins form projections on the surface of the virus.…”

“…Flaviviridae are a family of viruses whose genetic material is the (+)ssRNA molecule. They encode at least three structural proteins such as C (capsid), M/prM (vestibule) and E (envelope) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) ( 76 , 99 ). Flavivirus contains more than 70 viruses, including dengue virus (DENV), West Nile virus (WNV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), and avian Tembus virus (ATMUV) ( 100 , 101 ).…”

Mechanism of autophagy induced by activation of the AMPK/ERK/mTOR signaling pathway after TRIM22-mediated DENV-2 infection of HUVECs

“…TRIM69 degrades Lys104 amino acid residues of DENV NS3 by ubiquitinating its RING domain through E3 ubiquitin ligase activity to inhibit DENV replication [28]. The subgenomic RNA of DENV-2 inhibits RIG-I activation and IFN expression by binding to TRIM25 [29].…”