1.A.39 The Type C Influenza Virus CM2 Channel (CM2-C) Family
The mechanisms and functions of viral channel proteins have been reviewed by Fischer and Hsu (2011) and Fischer et al. (2012). The CM2 putative channel of type C influenza virus is 139 aas long and shows two putative TMSs. The first is a cleavage signal sequence. The mature, processed glycoprotein (115 aas) is a type I membrane protein with an extracellular N-terminus, glycosylated on Asn-26, a single central TMS, and a cytoplasmic C-terminus (Nout-Cin). It is a disulfide-linked homotetramer (Fischer and Sansom, 2002).
CM2 and a chimeric influenza A virus M2 protein (MCM), containing the CM2 transmembrane domain, could alter cytosolic pH when expressed from cDNAs, but only M2 and MCM, not CM2 could restore infectious virus production to M2-deficient influenza A viruses (Stewart and Pekosz 2012). Thus, while the CM2 ion channel activity is similar to that of M2, sequences in the extracellular and/or cytoplasmic domains play important roles in infectious virus production.