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.
References:
Strtak, A.C., J.L. Perry, M.N. Sharp, A.L. Chang-Graham, T. Farkas, and J.M. Hyser. (2019). Recovirus NS1-2 Has Viroporin Activity That Induces Aberrant Cellular Calcium Signaling To Facilitate Virus Replication. mSphere 4:.
Examples:
TC#	Name	Organismal Type	Example
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

1.A.125.1.2	Polyprotein of 2037 aas with the viroporin encoded within the ~ first 233 aas.		Polyprotein of Racaecavirus sp., an unclassified Riboviria

1.A.125.1.3	Polyprotein of 1991 aas including an N-terminal viroporin in ~ the first 233 aas, homologous to Ns1-2.		Polyprotein of marmot norovirus

1.A.125.1.4	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

1.A.125.1.5	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

1.A.125.1.6	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

1.A.125.1.7	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

Examples:
TC#	Name	Organismal Type	Example
1.A.125.2.1	HRAS-like suppressor 2 of 178 aas and 1 or 2 C-terminal TMSs.		*Suppressor of Cyprinus carpio* (common carp)**

1.A.125.2.2	Phospholipase A and acyltransferase 3-like of 170 aas and 2 C-terminal TMSs.		Phospholipase A of Neolamprologus brichardi

1.A.125.2.3	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.**

1.A.125.2.4	Uncharacterized protein of 345 aas and 2 C-terminal TMSs.		*UP of Zonotrichia albicollis* (white-throated sparrow)**