{Reference Type}: Journal Article
{Title}: Reduced vacuolar ATPase protects mice from Friend virus infection - an unintended but instructive effect in Hif-2afl mice.
{Author}: Schreiber T;Koll N;Padberg C;de Los Reyes B;Quinting T;Malyshkina A;Metzen E;Sutter K;Fandrey J;Winning S;
{Journal}: J Cell Sci
{Volume}: 137
{Issue}: 12
{Year}: 2024 Jun 15
{Factor}: 5.235
{DOI}: 10.1242/jcs.261893
{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-2α in macrophages during acute Friend murine leukemia retrovirus (FV) infection in C57BL/6 mice using a Cre/loxP system. Remarkably, mice with 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-2α 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.