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. 2024 Aug;9(8):2038-2050.
doi: 10.1038/s41564-024-01765-z. Epub 2024 Jul 29.

SARS-CoV-2-related bat viruses evade human intrinsic immunity but lack efficient transmission capacity

Mario A Peña-Hernández  1   2   3 , Mia Madel Alfajaro  3 , Renata B Filler  3 , Miyu Moriyama  1 , Emma L Keeler  2   3 , Zara E Ranglin  3 , Yong Kong  1 , Tianyang Mao  1 , Bridget L Menasche  3 , Madeleine C Mankowski  1   3 , Zhe Zhao  3 , Chantal B F Vogels  4 , Anne M Hahn  4 , Chaney C Kalinich  4 , Shuo Zhang  2   3 , Nicholas Huston  5 , Han Wan  5 , Rafael Araujo-Tavares  5 , Brett D Lindenbach  2 , Robert Homer  6 , Anna Marie Pyle  5   7   8 , David R Martinez  1 , Nathan D Grubaugh  4 , Benjamin Israelow  1   9 , Akiko Iwasaki  10   11   12   13 , Craig B Wilen  14   15
Affiliations

SARS-CoV-2-related bat viruses evade human intrinsic immunity but lack efficient transmission capacity

Mario A Peña-Hernández et al. Nat Microbiol. 2024 Aug.

Abstract

Circulating bat coronaviruses represent a pandemic threat. However, our understanding of bat coronavirus pathogenesis and transmission potential is limited by the lack of phenotypically characterized strains. We created molecular clones for the two closest known relatives of SARS-CoV-2, BANAL-52 and BANAL-236. We demonstrated that BANAL-CoVs and SARS-CoV-2 have similar replication kinetics in human bronchial epithelial cells. However, BANAL-CoVs have impaired replication in human nasal epithelial cells and in the upper airway of mice. We also observed reduced pathogenesis in mice and diminished transmission in hamsters. Further, we observed that diverse bat coronaviruses evade interferon and downregulate major histocompatibility complex class I. Collectively, our study demonstrates that despite high genetic similarity across bat coronaviruses, prediction of pandemic potential of a virus necessitates functional characterization. Finally, the restriction of bat coronavirus replication in the upper airway highlights that transmission potential and innate immune restriction can be uncoupled in this high-risk family of emerging viruses.

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