Suboptimal nucleotides in the infectious, pathogenic simian immunodeficiency virus clone SIVmac239

We analyzed virus sequences in two monkeys infected with SIVmac239 and two monkeys infected with SHIVnef that maintained high, persisting viral loads. Sequence changes were observed consistently at four loci in all four anima ls: a single nucleotide change in the Lys-tRNA primer binding site in the 5 ' long terminal repeat; two nucleotide changes that resulted in two amino a cid changes in the pol gene product; and a single nucleotide change in the region of the simian immunodeficiency virus genome where the rev and env ge nes overlap, resulting in changes in the predicted amino acid sequences of both gene products. None of these mutations were seen in short-term culture s of CEM x 174 cells infected with SIVmac239 or SHIVnef. At all four positi ons in all four animals, the new sequences represented consensus sequences for primate lentiviruses, whereas the inoculum sequences at these four loci have either never been or rarely been reported outside of SIVmac239. Thus, although cloned SIVmac239 is consistently pathogenic and consistently indu ces high viral load set points, it is clearly less than optimal at these fo ur nucleotide positions.