Decomposition of L-glutamine and accumulation of ammonium in cell culture media inhibit infectivity of influenza viruses

Nathanael B Kegel; Andreas Kaufmann; Mikhail Matrosovich; Stefan Bauer; Jens Dorna

doi:10.1016/j.virol.2024.110314

Decomposition of L-glutamine and accumulation of ammonium in cell culture media inhibit infectivity of influenza viruses

Virology. 2024 Nov 20:602:110314. doi: 10.1016/j.virol.2024.110314. Online ahead of print.

Authors

Nathanael B Kegel¹, Andreas Kaufmann², Mikhail Matrosovich³, Stefan Bauer², Jens Dorna⁴

Affiliations

¹ Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany. Electronic address: kegel@uni-marburg.de.
² Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany.
³ Institute of Virology, Philipps-Universität Marburg, 35043, Marburg, Germany.
⁴ Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany; CSL Innovation GmbH, Emil-von-Behring, Straße 76, 35041, Marburg, Germany.

PMID: 39579506
DOI: 10.1016/j.virol.2024.110314

Abstract

Cationic lysosomotropic molecules such as ammonium salts and chloroquine inhibit influenza A virus (IAV) infection in cell culture by counteracting endosomal acidification and hampering viral-endosomal fusion. Here, we studied the effects of storage of L-glutamine-supplemented cell culture media on accumulation of ammonium and inhibition of IAV infection. The storage-related inhibitory effect was observed for DMEM and OptiMEM media but not for RPMI medium, and was more pronounced for IAV with pH-stable hemagglutinin. Our results highlight the importance to consider potential presence of virus-inhibiting lysosomotropic agents and/or their production in culture media with negative effect on influenza virus infection.

Keywords: Ammonium; Cell culture; Endosomal acidification; Influenza A virus; L-glutamine; Virus inactivation.