15th Conference on Retroviruses and Opportunistic Infections Boston, Massachusetts - February 3-6, 2008

Conf Retrovir Opportunistic Infect 2008 Feb 3-6;15: (abstract no. 20)

Thaidra Gaufin ¹, M Pattison¹, C Stoulig¹, R Gautam¹, M Barnes¹, C Monjure¹, M Marx¹, D Montefiori², C Apetrei¹, and I Pandrea^1
1Tulane Natl Primate Res Ctr, Covington, LA, US and ²Duke Univ, Durham, NC, US

BACKGROUND: Simian immunodeficiency virus (SIV) -infected African nonhuman primates do not progress to AIDS in spite of active and persistent viral replication of the same magnitude or higher than in pathogenic infections. Anti-SIV titers are lower in SIV-infected African nonhuman primates than in rhesus macaques. Some authors suggest that the high viral loads observed in chronic natural SIV infections may result from these lower anti-SIV responses, which would imply a role of antibodies in controlling viral loads. We investigated the effect of antibody responses on the outcome of acute and chronic SIV_agm replication in African green monkeys.

METHODS: We inoculated 10 African green monkeys with 300 TCID₅₀ of SIV_agm.sab, 4 of which received 50 mg/kg of an anti-CD20 antibody (Rituxan, gift from Genentech) every 21 days, starting from day 7 post-infection. Remaining African green monkeys were used as controls and received SIV_agm only. Viral loads in plasma and tissues were determined by real-time polymerase chain reaction (RT-PCR) and in situ hybridization (ISH). Dynamics of the major lymphocyte subsets were measured in periph, and apoptosis of T cells were investigated by flow cytometry and immunohistochemistry (IHC). Serology was performed to compare the differences in emergence of anti-SIV antibodies between the 2 groups.

RESULTS: All Rituxan-treated African green monkeys were successfully depleted of CD20 cells in peripheral blood, lymph nodes, and intestine, as illustrated by the dynamics of CD20+ and CD79a cells (flow-cytometry and IHC). There was no significant difference in viral loads between CD20-depleted African green monkeys and control monkeys: during acute infection, peak viral loads ranged from 10⁷ to 10⁸ copies/mL; during chronic infection, set-point values ranged from 10⁴ to 10⁵ SIV RNA copies/mL. A similar degree of acute CD4 T cell depletion in the intestine was observed in treated and non-treated animals. SIV_agm seroconversion was delayed in the CD20-depleted African green monkeys compared to the controls. There was a significant difference in both timing and magnitude of neutralizing antibody responses in CD20-depleted African green monkeys compared to controls. CD20 depletion resulted in effacing the histological structure of the germinal centers in the lymph nodes and Payer’s patches. No viral trapping was observed in these modified histological structures.

CONCLUSIONS: Our study shows that humoral immune responses play no significant role in the control of SIV viral replication during acute and chronic SIV_agm infection in the natural host.

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2008-02-03
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