Hobbs, A. | bioRxiv Science

bioRxiv2022

Astrocyte mitochondria produce nitric oxide from nitrite to modulate cerebral blood flow during brain hypoxia

In low oxygen conditions, increases in cerebral blood flow maintain brain oxygen delivery but the mechanisms underlying hypoxia-induced dilations of cerebral vasculature are incompletely understood. Here we show that astrocytes accumulate nitrite and in response to hypoxia produce nitric oxide via mitochondrial reduction of nitrite by a molybdenum-containing enzyme sulfite oxidase. These data suggest that astrocytes can modulate cerebral blood flow in accord with brain tissue oxygenation via mitochondrial production of nitric oxide.

neuroscience↗

bioRxiv2021

VPS29 exerts opposing effects on endocytic viral entry

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, was required for infection by HCoV-OC43, SARS-CoV-2, other endemic and pandemic threat coronaviruses as well as ebolavirus. 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. VPS29 deficiency caused changes 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 viral susceptibility and identify a host pathway that could serve as a pharmaceutical target for intervention in zoonotic viral diseases.

microbiology↗