1. Reduced vacuolar ATPase protects mice from Friend virus infection - an unintended but instructive effect in Hif-2afl mice.
- Author
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Schreiber, Timm, Koll, Nora, Padberg, Claudia, de los Reyes, Buena, Quinting, Theresa, Malyshkina, Anna, Metzen, Eric, Sutter, Kathrin, Fandrey, Joachim, and Winning, Sandra
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VIRUS diseases , *ADENOSINE triphosphatase , *HYPOXIA-inducible factors , *MOUSE leukemia , *MICE , *GABA receptors - Abstract
During acute viral infections, innate immune cells invade inflamed tissues and face hypoxic areas. Hypoxia-inducible factors (HIFs) adapt cellular responses towards these conditions. We wanted to investigate the effects of a loss of HIF-2 α in macrophages during acute Friend murine leukemia retrovirus (FV) infection in C57BL/6 mice using a Cre/loxP system. Remarkably, micewith floxed Hif-2a (Hif-2afl; Hif-2a is also known as Epas1) did not show any signs of FV infection independent of Cre activity. This prevented a detailed analysis of the role of macrophage HIF-2 α for FV infection but allowed us to study a model of unexpected FV resistance. Hif-2afl mice showed a significant decrease in the expression of the Atp6v1e2 gene encoding for the E2 subunit of the vacuolar H+-ATPase, which resulted in a decreased acidification of lysosomes and limited virus entry into the cell. These findings highlight that the insertion of loxP sites is not always without functional consequences and has established a phenotype in the floxed Hif-2a mouse, which is not only unexpected, but unwanted and is of relevance for the use of this mouse strain in (at least virus) experiments. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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