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. Our group identified and characterized an SIVsmm strain (SIVsmmD215) that is highly susceptible to neutralization by autologous and heterologous sera. We investigated the impact of antibody neutralization on SIV replication using this neutralizing strain. Thirteen Rh were inoculated with 100 TCID50 of SIVsmD215. Seven were treated with 50 mg/kg with rituxan (an anti-CD20 antibody) at days ?7, 14, 35 and 56 post-SIVsmmD215 infection. The other 6 were used as a controls and received SIVsmmD215 only. The dynamics of viral replication (VL) and major lymphocyte subsets were measured in peripheral blood, lymph nodes (LNs) and intestine. Serology was performed to compare the differences in emergence of anti-SIV antibodies between the two groups. All the animals in the study group were successfully depleted of CD20 cells in peripheral blood. Three animals only partially depleted CD20 cells in the LNs and the intestine. There was no significant difference in VLs between CD20 depleted Rh and control monkeys: peak VLs ranged from 10^6 to 3 x 10^8 SIV RNA copies/ml. During the chronic phase of infection, both groups showed similar control of viral replication (set-point VLs of 10^2 to 10^4 SIV RNA copies/ml). There was a tendency for lower set-point VLs in the group of CD20-depleted Rh. SIVsmm seroconversion was delayed in the animals for which the CD20 depletion was complete in the intestine and LNs. Cellular immune responses were similar at late time-points;higher in CD20-depleted macaques early in infection between CD20-depleted Rh comparing to the control group and may have accounted for the control of VL during the post-peak stage. In conclusion, we have shown that CD20 depletion plays no significant role in the control of SIV viral replication during the chronic stage of infection. Although depletion is complete in the periphery in all the animals, the lack of antibody production is predicted by the efficacy of CD20 depletion at the main site of viral replication
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