RRC ID 54386
Author Abernathy E, Mateo R, Majzoub K, van Buuren N, Bird SW, Carette JE, Kirkegaard K.
Title Differential and convergent utilization of autophagy components by positive-strand RNA viruses.
Journal PLoS Biol
Abstract Many viruses interface with the autophagy pathway, a highly conserved process for recycling cellular components. For three viral infections in which autophagy constituents are proviral (poliovirus, dengue, and Zika), we developed a panel of knockouts (KOs) of autophagy-related genes to test which components of the canonical pathway are utilized. We discovered that each virus uses a distinct set of initiation components; however, all three viruses utilize autophagy-related gene 9 (ATG9), a lipid scavenging protein, and LC3 (light-chain 3), which is involved in membrane curvature. These results show that viruses use noncanonical routes for membrane sculpting and LC3 recruitment. By measuring viral RNA abundance, we also found that poliovirus utilizes these autophagy components for intracellular growth, while dengue and Zika virus only use autophagy components for post-RNA replication processes. Comparing how RNA viruses manipulate the autophagy pathway reveals new noncanonical autophagy routes, explains the exacerbation of disease by starvation, and uncovers common targets for antiviral drugs.
Volume 17(1)
Pages e2006926
Published 2019-1-1
DOI 10.1371/journal.pbio.2006926
PII pbio.2006926
PMID 30608919
PMC PMC6334974
MeSH Autophagy / genetics* Autophagy-Related Proteins / metabolism Cell Line Dengue / virology Dengue Virus / genetics Dengue Virus / physiology HeLa Cells Humans Poliomyelitis / virology Poliovirus / genetics Poliovirus / physiology RNA Viruses / genetics* RNA Viruses / metabolism RNA Viruses / physiology* RNA, Viral Virus Diseases / genetics Virus Replication Zika Virus / genetics Zika Virus / physiology Zika Virus Infection / virology
IF 7.076
Times Cited 23
Resource
Mice RBRC02975