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. To better understand which factors govern the levels of viral loads in early lentiviral infections of primates, we developed a model that allows distinguishing between the influence of host and viral factors on viremia. Herein we report that two species of AGMs (Chlorocebus sabaeus and C. pygerythrus) infected with their respective wild type SIVagm viruses (SIVagm.sab92018 and SIVagm.ver644) consistently showed reproducible differences in viremia during primary infection, but not at later stages of infection. Cross-infections of SIVagm.sab92018 and SIVagm.ver644 into, respectively, C. pygerythrus and C. sabaeus revealed that the dynamics of viral replication during primary infection was dependent of the viral strain used for the infection, but not of the host. Hence, the kinetics of SIVagm.sab92018 and SIVagm.ver644 were similar in either sabaeus or vervet animals indicating that the difference in viremia between the two groups during the early phase of infection was not associated with the host. Coreceptor usage for these two strains showed a larger co-receptor repertoire for SIVagm.sab92018, which is able to efficiently use CXCR4 in addition to CCR5, in contrast to SIVagm.ver644, which showed a classical CCR5 coreceptor usage pattern. These differences could not be explained by different charges of the V3 loop between SIVagm.sab92018 and SIVagm.ver644. In conclusion, our study showed that the extent of virus replication during the primary infection is primarily dependent on viral determinants.
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