VPS29 Exerts Opposing Effects on Endocytic Viral Entry.
mBio
; 13(2): e0300221, 2022 04 26.
Article
in English
| MEDLINE | ID: covidwho-1714353
ABSTRACT
Emerging zoonotic viral pathogens threaten global health, and there is an urgent need to discover host and viral determinants influencing infection. We performed a loss-of-function genome-wide CRISPR screen in a human lung cell line using HCoV-OC43, a human betacoronavirus. One candidate gene, VPS29, a component of the retromer complex, was required for infection by HCoV-OC43, SARS-CoV-2, other endemic- and pandemic-threat coronaviruses, as well as ebolavirus. Notably, we observed a heightened requirement for VPS29 by the recently described Omicron variant of SARS-CoV-2 compared to the ancestral variant. However, VPS29 deficiency had no effect on certain other viruses that enter cells via endosomes and had an opposing, enhancing effect on influenza A virus infection. Deficiency in VPS29 or other retromer components caused changes in endosome morphology and acidity and attenuated the activity of endosomal proteases. These changes in endosome properties caused incoming coronavirus, but not influenza virus particles, to become entrapped therein. Overall, these data show how host regulation of endosome characteristics can influence cellular susceptibility to viral infection and identify a host pathway that could serve as a pharmaceutical target for intervention in zoonotic viral diseases. IMPORTANCE These data identify a host pathway by which VPS29 and associated factors control the endosomal environment in a manner that influences susceptibility to viral infection. This pathway could serve as a pharmaceutical target for intervention in zoonotic viral diseases, including those caused by coronaviruses, influenza viruses, and filoviruses, all of which are pandemic threats. Our findings show how host regulation of endosome characteristics can influence viral susceptibility in both a positive and negative manner.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Influenza A virus
/
Coronavirus OC43, Human
/
COVID-19
Type of study:
Experimental Studies
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
MBio
Year:
2022
Document Type:
Article
Affiliation country:
Mbio.03002-21
Similar
MEDLINE
...
LILACS
LIS