Extensively deleted simian immunodeficiency virus (SIV) DNA in macaques inoculated with supercoiled plasmid DNA encoding full-length SIVmac239

Using long-distance DNA PCR, we prospectively followed rhesus monkeys that had been inoculated intramuscularly with supercoiled plasmid DNA encoding i ntact simian immunodeficiency virus (SIV). From 4 to 10 weeks postinoculati on 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 freque ncy of deleted proviral genomes was similar in PBMC and lymph nodes. The la tter, however, harbored significantly more full-length proviral DNA than PB MC, consistent with the lack of effective antiviral cytotoxic T-cell activi ty in lymph nodes described by others during human immunodeficiency virus i nfection. After the macaques progressed to AIDS, full-length proviral DNA b ecame equally abundant in lymph nodes and in PBMC. We have demonstrated tha t although a single molecular species of proviral DNA was inoculated, genom ic diversity was detected within a short time, thus confirming the genetic instability of the SIV genome in vivo. (C) 2001 Academic Press.