1.A.83 The SV40 Virus Viroporin VP2 (SV40 VP2) Family

For nonenveloped viruses such as Simian Virus 40, the mechanism used to translocate viral components across membranes involves viroporins. The minor structural proteins, VP2 and VP3, which are products of the same gene and differ in that VP2 has 118 aas at the N-terminus that are lacking in VP3, apparently act as membrane proteins during infection. Giorda et al. (2012) purified VP2 and VP3, and both were found to form pores in host cell membranes. To identify possible membrane domains, individual hydrophobic domains from VP2 and VP3 were expressed in a model protein and tested for their ability to integrate into membranes. Several domains from the late proteins supported endoplasmic reticulum membrane insertion as transmembrane domains. Mutations in VP2 and VP3 were engineered that inhibited membrane insertion and pore formation. When these mutations were introduced into the viral genome, viral propagation was inhibited. Thus, the viroporin activities of VP2 and VP3 were inhibited by targeted disruptions of individual hydrophobic domains, and the loss of membrane disruption activity impaired viral infection (Giorda et al. 2012).