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Significance It is well known that genetic differences among individuals can influence their susceptibility to infectious disease. Our results, using New World arenavirus-infected mice heterozygous for the α1S chain of the VGCC, human cells heterozygous for a mutation of this chain, and drugs that target this receptor, highlight the influence of genetic background on the outcome of infection and zoonoses. These findings also confirm the use of VGCCs as potential therapeutic targets and pave the way for understanding the relationship between genetics, susceptibility to infection, and antiviral drug efficacy.

CACNA1S haploinsufficiency confers resistance to New World arenavirus infection