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CACNA1S haploinsufficiency confers resistance to New World arenavirus infection.

ABSTRACT: Understanding the genetics of susceptibility to infectious agents is of great importance to our ability to combat disease. Here, we show that voltage-gated calcium channels (VGCCs) are critical for cellular binding and entry of the New World arenaviruses Junín and Tacaribe virus, suggesting that zoonosis via these receptors could occur. Moreover, we demonstrate that ?1s haploinsufficiency renders cells and mice more resistant to infection by these viruses. In addition to being more resistant to infection, haploinsufficient cells and mice required a lower dosage of VGCC antagonists to block infection. These studies underscore the importance of genetic variation in susceptibility to both viruses and pharmaceutics.

SUBMITTER: Sarute N

PROVIDER: S-EPMC7431027 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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CACNA1S haploinsufficiency confers resistance to New World arenavirus infection.

Sarute Nicolás N Ross Susan R SR

Proceedings of the National Academy of Sciences of the United States of America 20200727 32

Understanding the genetics of susceptibility to infectious agents is of great importance to our ability to combat disease. Here, we show that voltage-gated calcium channels (VGCCs) are critical for cellular binding and entry of the New World arenaviruses Junín and Tacaribe virus, suggesting that zoonosis via these receptors could occur. Moreover, we demonstrate that α1s haploinsufficiency renders cells and mice more resistant to infection by these viruses. In addition to being more resistant to ...[more]

PMID: 32719120

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