HIV-1 evolves from a macrophage-tropic noncytopathic virus at early stages of infection to a T-cell- tropic, syncytia-inducing virus population with progression to AIDS. It was determined whether simian immunodeficiency virus (SIV) infection in macaques is associated with a similar shift in viral tropism and replication properties by obtaining isolates from pig-tailed macaques infected with our pathogenic molecular clone of SIV/Mne (clone 8). The virus that predominated early after infection is a macrophage-tropic virus that replicates with relatively low efficiency in human T-cell lines. As macaques progress to AIDS, the isolates exhibit enhanced replication and an expanded host range for T-cell lines, but replicate less efficiently in primary macrophages. Dr. J. Overbaugh at the University of Washington has shown that the V3 sequences were generally conserved between the early and late variants, suggesting that changes in SIV/Mne tropism and cytopathicity were not due to alterations in V3. Another domain of SIV/Mne env, for example V1 or V4, may serve as the functional equivalent of HIV-1 V3. The SIV infection of macaques may thus provide a valuable system for determining whether the T-cell tropic, rapidly replicating, syncytia-inducing viruses present late in infection represent variants that are more pathogenic in the host. In any case, additional studies of chimeras between the late, cytopathic SIV/Mne variants and SIV/Mne CL 8 will be required to define the precise determinants for the phenotypic changes observed.
