This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.We identified and characterized an SIVsmm strain (SIVsmmD215) that is highly susceptible to neutralization. Here, we investigated the impact of antibody neutralization on SIV replication using this neutralizing strain. Eight Rh were inoculated with 100 TCID50 of SIVsmD215. Four were treated with 50 mg/kg of rituxan (an anti-CD20 antibody) at days 7, 14, 35 and 56 post-infection. The other four were used as controls and received SIVsmmD215 only. The dynamics of viral replication and major lymphocyte subsets were measured in peripheral blood, lymph nodes 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. Two animals only partially depleted CD20 cells in the LNs and the intestine. There was no significant difference in viral replication between CD20 depleted Rh and controls: peak viral loads ranged from 8 x 10^5 to 3 x 10^7 SIV RNA copies/ml in the CD20-depleted monkeys and from 8 x 10^6 to 9 x 10^7 SIV RNA copies/ml in control Rh. During the chronic phase of infection, both groups showed similar control of viral replication (set-point values ranging from 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 comparing to controls. SIVsmm seroconversion was delayed in the animals for which the CD20 depletion was complete in the intestine and LNs. 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. We showed that 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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