Reduced Vacuolar ATPase Protects Mice from Friend Virus Infection - an Unintended but Instructive Effect in Hif-2afl Mice

Overview

Journal J Cell Sci

Specialty Cell Biology

Date 2024 Jun 10

PMID 38856651

Authors

Timm Schreiber

Nora Koll

Claudia Padberg

Buena de Los Reyes

Theresa Quinting

Anna Malyshkina

Eric Metzen

Kathrin Sutter

Joachim Fandrey

Sandra Winning

Affiliations

Soon will be listed here.

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.

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