Extensively deleted simian immunodeficiency virus (SIV) DNA in macaques inoculated with supercoiled plasmid DNA...

Using long-distance DNA PCR, we prospectively followed rhesus monkeys that had been inoculated intramuscularly with supercoiled plasmid DNA encoding intact simian immunodeficiency virus (SIV). From 4 to 10 weeks postinoculation onward, we detected extensively deleted proviral genomes along with full-length viral genomes in peripheral blood mononuclear cells (PBMC) in adult macaques. During their chronic asymptomatic phase of infection, the frequency of deleted proviral genomes was similar in PBMC and lymph nodes. The latter, however, harbored significantly more full-length proviral DNA than PBMC, consistent with the lack of effective antiviral cytotoxic T-cell activity in lymph nodes described by others during human immunodeficiency virus infection. After the macaques progressed to AIDS, full-length proviral DNA became equally abundant in lymph nodes and in PBMC. We have demonstrated that although a single molecular species of proviral DNA was inoculated, genomic diversity was detected within a short time, thus confirming the genetic instability of the SIV genome in vivo.