The SIVmac239 Pr55^Gag isoform, SIV p43, suppresses proteolytic cleavage of Pr55^Gag

In human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) the gag gene encodes the precursor polyprotein Pr55^Gag, which is cleaved by the viral protease to produce the major structural proteins. Recently, it has been shown that HIV and SIV gag RNAs contain internal ribosome entry sites (IRESs) that mediate translation of Pr55^Gag [Pr57^Gag in HIV type 2 (HIV-2)] isoforms. Previously, we demonstrated that SIVmac239 p43(-), a mutant that does not express the Pr55^Gag isoform, SIV p43, replicates more efficiently than wild-type (WT) SIVmac239 in cell culture. In this study, we characterize SIVmac239 p43(-) virion production and demonstrate that, in the absence of SIV p43, cleavage of Pr55^Gag is increased in budded virions, resulting in a higher percentage of mature particles. Additionally, intracellular cleavage of Pr55^Gag is increased in SIVmac239 p43(-), suggesting that SIV p43 suppresses premature cleavage of Pr55^Gag by the viral protease.