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 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.

了解传染病易感性的遗传学对我们抵抗疾病的能力至关重要。在这里，我们显示电压门控钙通道（VGCC）对于细胞结合和进入新大陆砂粒病毒Junín和Tacaribe病毒至关重要，表明可能通过这些受体发生人畜共患病。此外，我们证明了α1s单倍体不足使细胞和小鼠对这些病毒的感染更具抵抗力。除了对感染有更强的抵抗力以外，单倍体不足的细胞和小鼠还需要更低剂量的VGCC拮抗剂来阻断感染。这些研究强调了遗传变异对病毒和药物敏感性的重要性。