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.
Tulane Virus polyprotein of 1447 aas with the first 233 aas corresponding to the viroporin, NS1-2. It has two TMS near the C-terminus of this viroporin (Strtak et al. 2019). See family description for more details.
NS1-2 of Tulane virus
Polyprotein of 2037 aas with the viroporin encoded within the ~ first 233 aas.
Polyprotein of Racaecavirus sp., an unclassified Riboviria
Polyprotein of 1991 aas including an N-terminal viroporin in ~ the first 233 aas, homologous to Ns1-2.
Polyprotein of marmot norovirus
Nonstructural polyprotein of 1943 aas and 1 or 2 C-terminal TMSs in the first 233 aas of this polyprotein which probably code for a viroporin (see family description as well as 1.A.125.1.1).
Polyprotein of Norovirus GVI
N-terminal leader protein p48 of 398 aas and possibly 1 or 2 C-terminal TMSs. Possible viroporin based on sequence similarity with TC# 1.A.125.1.1.
p48 of Norovirus GI
Polyprotein of 2208 aas and at least 4 TMSs, two near the N-terminus of the polyprotein where a viroporin may be present.
Polyprotein of Guangdong greater green snake calicivirus
Polyprotein of 2386 aas and 2 probable TMSs at the C-terminal end of the first 260 aas where the viroporin may be.
Polyprotein of Zhejiang gunthers frog calicivirus 2
HRAS-like suppressor 2 of 178 aas and 1 or 2 C-terminal TMSs.
Suppressor of Cyprinus carpio (common carp)
Phospholipase A and acyltransferase 3-like of 170 aas and 2 C-terminal TMSs.
Phospholipase A of Neolamprologus brichardi
Lecithin retinol acyltransferase family protein of 202 aas with two moderately hydrophobic peaks (N-terminal) and two amphipathic peaks (C-terminal).
Acyltransferase of Cupriavidus sp.
Uncharacterized protein of 345 aas and 2 C-terminal TMSs.
UP of Zonotrichia albicollis (white-throated sparrow)