Preexisting Infection with Human T-Cell Lymphotropic Virus Type 2 neither Exacerbates nor Attenuates Simian Immunodeficiency Virus SIV mac251 Infection in Macaques

• Published in: Journal of virology 2010-03, Vol.84 (6), p.3043-3058
• Main Authors: Gordon, Shari N., Weissman, Anna R., Cecchinato, Valentina, Fenizia, Claudio, Ma, Zhong-Min, Lee, Tzong-Hae, Zaffiri, Lorenzo, Andresen, Vibeke, Parks, Robyn Washington, Jones, Kathryn S., Heraud, Jean Michel, Ferrari, Maria Grazia, Chung, Hye Kyung, Venzon, David, Mahieux, Renaud, Murphy, Edward L., Jacobson, Steven, Miller, Christopher J., Ruscetti, Francis W., Franchini, Genoveffa
• Format: Article
• Language: English
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/JVI.01655-09

Coinfection with human T-cell lymphotropic virus type 2 (HTLV-2) and human immunodeficiency virus type 1 (HIV-1) has been reported to have either a slowed disease course or to have no effect on progression to AIDS. In this study, we generated a coinfection animal model and investigated whether HTLV-2 could persistently infect macaques, induce a T-cell response, and impact simian immunodeficiency virus SIV mac251 -induced disease. We found that inoculation of irradiated HTLV-2-infected T cells into Indian rhesus macaques elicited humoral and T-cell responses to HTLV-2 antigens at both systemic and mucosal sites. Low levels of HTLV-2 provirus DNA were detected in the blood, lymphoid tissues, and gastrointestinal tracts of infected animals. Exposure of HTLV-2-infected or naïve macaques to SIV mac251 demonstrated comparable levels of SIV mac251 viral replication, similar rates of mucosal and peripheral CD4 + T-cell loss, and increased T-cell proliferation. Additionally, neither the magnitude nor the functional capacity of the SIV-specific T-cell-mediated immune response was different in HTLV-2/SIV mac251 coinfected animals versus SIV mac251 singly infected controls. Thus, HTLV-2 targets mucosal sites, persists, and importantly does not exacerbate SIV mac251 infection. These data provide the impetus for the development of an attenuated HTLV-2-based vectored vaccine for HIV-1; this approach could elicit persistent mucosal immunity that may prevent HIV-1/SIV mac251 infection.