This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Currently, there is no animal model for HIV-1 infection and disease because the virus is highly specific for humans. Macaques are generally resistant to HIV-1, with the exception being pig-tailed macaques. Our lab showed that pig-tailed macaques are unable to express functional isoforms of TRIM5-alpha, which has been identified as a host factor that restricts the replication of HIV-1 in rhesus monkeys. Therefore, it is possible that HIV-1 will only need to overcome restriction by another host factor, APOBEC3G/F, to replicate successfully in pig-tailed macaques. To test this hypothesis, we collaborated with Dr. J. Kimata of Baylor College of Medicine, who engineered an HIV-1 clone that includes the vif gene of SIVmne, allowing it to counteract APOBEC3G/F-mediated restriction. This chimeric virus, HSIV-vif, is 96% HIV-1 and 4% SIV. It replicates in stimulated pig-tailed macaque blood cells as efficiently as SIVmne. In another pilot study, we inoculated 2 juvenile pig-tailed macaques intravenously with HSIV-vif. Although both animals became infected, plasma viremia did not sustain beyond 10 months after infection. Since newborn animals are more susceptible to lentiviral infection and disease, we inoculated two newborn pig-tail macaques with HSIV-vif. Preliminary results indicate that both animals were infected, with a peak plasma viral load of 0.5-1x105 copies/ml. It is too early to tell if plasma viremia will sustain, but we will continue to monitor these animals to determine their setpoint viral load and the evolution of viral species.
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