1.A.125. The Calicivirus NS1-2 Viroporin (NS1-2 VP) Family
Enteric viruses in the Caliciviridae family cause acute gastroenteritis in humans and animals. A common strategy among enteric viruses, including rotaviruses and enteroviruses, is to encode a viroporin that is targeted to the endoplasmic reticulum (ER) and disrupts host calcium (Ca2+) homeostasis. The nonstructural proteins of caliciviruses and enteroviruses, including the calicivirus NS1-2 protein and the 2B viroporin of enteroviruses. Caliciviruses alter Ca2+ homeostasis for virus replication, and the NS1-2 protein has viroporin activity like its enterovirus counterpart (Strtak et al. 2019). Tulane virus (TV), a rhesus enteric calicivirus was used to examine Ca2+ signaling during infection and determine whether NS1-2 has viroporin activity that disrupts Ca2+ homeostasis. TV increased Ca2+ signaling during infection and increased cytoplasmic Ca2+ levels as are important for efficient replication. Further, TV NS1-2 localizes to the endoplasmic reticulum, the predominant intracellular Ca2+ store, and the NS2 region has characteristics of a viroporin domain. NS1-2 had viroporin activity in a classic bacterial functional assay and caused aberrant Ca2+ signaling when expressed in mammalian cells, but truncation of the VPD abrogated these activities. Thus, the NS2 region of NS1-2 is a viroporin, suggesting that enteric viruses, including those within Caliciviridae, exploit host Ca2+ signaling to facilitate their replication (Strtak et al. 2019). The viroporin of Tulane virus, a rhesus calicivirus, corresponds to the first 233 aas with 2 C-terminal TMSs of the polyprotein cited under TC# 1.A.125.1.1.