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) SIVmac239 and molecular clones of HIV-1 that differ in phenotypic properties controlled by the env ge ne, HIV-1(SF33) is a T-cell-fine-tropic virus which induces syncytia, and HIV-1(SF162) is a macrophage-tropic virus that does not induce syn cytia, A DNA fragment encoding tat, rev, and env (gp160) of SIVmac239 has been replaced with the counterpart genetic region of HIV-1(SF33) a nd HIV-1(SF162) to derive chimeric recombinant simian/human immunodefi ciency virus (SHIV) strains SHIVSF33 and SHIVSF162, respectively, In t he acute infection stage, macaques inoculated with SHIVSF33 had levels of viremia similar to macaques infected with SIVmac239, whereas virus loads were 1/10th to 1/100th those in macaques infected with SHIVSF16 2. Of note is the relatively small amount of virus detected in lymph n odes of SHIVSF162-infected macaques. In the chronic infection stage, m acaques infected with SHIVSF33 also showed higher virus loads than mac aques infected with SHIVSF162 Virus persists for over 1 year, as demon strated by PCR for amplification of viral DNA in all animals and by vi rus isolation in some animals. Antiviral antibodies, including antibod ies to the HIV-1 env glycoprotein (gp160), were detected; titers of an tiviral antibodies were higher in macaques infected with SHIVSF33 than in macaques infected with SHIVSF162 Although virus has persisted for over 1 year after inoculation, these animals have remained healthy wit h 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.