Persistent infection of rhesus macaques with T-cell-line-tropic and macrophage-tropic clones of simian/human immunodeficiency viruses (SHIV)

To elucidate the functions of human immunodeficiency virus type 1 (HIV-1) genes in a nonhuman primate model, we have constructed infectious recombinant viruses (chimeras) between the pathogenic molecular clone of simian immunodeficiency virus (SIV) SIV(mac239) and molecular clones of HIV-1 that differ in phenotypic properties controlled by the env gene. HIV-1(SF33) is a T-cell-line-tropic virus which induces syncytia, and HIV-1(SF162) is a macrophage-tropic virus that does not induce syncytia. A DNA fragment encoding tat, rev, and env (gp160) of SIV(mac239) has been replaced with the counterpart genetic region of HIV-1(SF33) and HIV-1(SF162) to derive chimeric recombinant simian/human immunodeficiency virus (SHIV) strains SHIV(SF33) and SHIV(SF162) respectively. In the acute infection stage, macaques inoculated with SHIV(SF33) had levels of viremia similar to macaques infected with SIV(mac239), whereas virus loads were 1/10th to 1/100th those in macaques infected with SHIV(SF162). Of note is the relatively small amount of virus detected in lymph nodes of SHIV(SF162)-infected macaques. In the chronic infection stage, macaques infected with SHIV(SF33) also showed higher virus loads than macaques infected with SHIV(SF162). Virus persists for over 1 year, as demonstrated by PCR for amplification of vital DNA in all animals and by virus isolation in some animals. Antiviral antibodies, including antibodies to the HIV-1 env glycoprotein (gp160), were detected; titers of antiviral antibodies were higher in macaques infected with SHIV(SF33) than in macaques infected with SHIV(SF162). Although virus has persisted for over 1 year after inoculation, these animals have remained healthy with no signs of immunodeficiency. These findings demonstrate the utility of the SHIV/macaque model for analyzing HIV-1 env gene functions and for evaluating vaccines based on HIV-1 env antigens.