SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells, 2023, Huot et al

SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA generally becomes undetectable in upper airways after a few days or weeks postinfection. Here we used a model of viral infection in macaques to address whether SARS-CoV-2 persists in the body and which mechanisms regulate its persistence.

Replication-competent virus was detected in bronchioalveolar lavage (BAL) macrophages beyond 6 months postinfection. Viral propagation in BAL macrophages occurred from cell to cell and was inhibited by interferon-γ (IFN-γ). IFN-γ production was strongest in BAL NKG2r+CD8+ T cells and NKG2Alo natural killer (NK) cells and was further increased in NKG2Alo NK cells after spike protein stimulation. However, IFN-γ production was impaired in NK cells from macaques with persisting virus. Moreover, IFN-γ also enhanced the expression of major histocompatibility complex (MHC)-E on BAL macrophages, possibly inhibiting NK cell-mediated killing. Macaques with less persisting virus mounted adaptive NK cells that escaped the MHC-E-dependent inhibition.

Our findings reveal an interplay between NK cells and macrophages that regulated SARS-CoV-2 persistence in macrophages and was mediated by IFN-γ.

https://www.nature.com/articles/s41590-023-01661-4

 

Am article in Nature related to these findings https://www.nature.com/articles/s41590-023-01679-8.

 

Lecture by Nicolas Huot (conference thread).

https://www.youtube.com/watch?v=gEsjR2y6fzs

 

10 min talk by Nicholas Huot at the PolyBio Spring 2024 Symposium.