Hantaviruses chronically infect rodent, shrew, mole, and bat reservoirs worldwide. Zoonotic transmission of hantaviruses to humans typically occurs through exposure to aerosolized rodent excreta and can lead to severe disease. For example, Andes virus (ANDV) and Sin Nombre virus (SNV) are causative agents of hantavirus cardiopulmonary syndrome (HCPS), and Hantaan virus (HTNV), Puumala virus (PUUV), and Seoul virus (SEOV) cause hemorrhagic fever with renal syndrome (HFRS). The envelope-anchored glycoproteins, Gn and Gc, are produced by enzymatic cleavage of the glycoprotein precursor (GPC) protein encoded in the M segment and are jointly responsible for orchestrating host cell entry and fusion.