Preexisting infection with human T-cell lymphotropic virus type 2 neither exacerbates nor attenuates simian immunodeficiency virus SIVmac251 infection in macaques.

Shari N Gordon (1) , Anna R Weissman (1) , Valentina Cecchinato (1) , Claudio Fenizia (1) , Zhong-Min Ma (2) , Tzong-Hae Lee (3) , Lorenzo Zaffiri (1) , Vibeke Andresen (1) , Robyn Washington Parks (1) , Kathryn S Jones (4) , Jean-Michel Heraud (5) , Maria Grazia Ferrari (6) , Hye Kyung Chung (6) , David Venzon (7) , Renaud Mahieux (2) , Edward L Murphy (3, 8) , Steven Jacobson (9) , Christopher J Miller (10) , Francis W Ruscetti (4) , Genoveffa Franchini (1)

1 Animal Models and Retroviral Vaccines Section
2 Virologie humaine
3 Blood Systems Research Institute
4 Basic Research Program, SAIC-Frederick, Inc.
5 Institut Pasteur de Madagascar
6 Advanced BioScience Laboratories, Inc.
7 Biostatistics and Data Management Section
8 Department of Laboratory Medicine and of Epidemiology and Biostatistics
9 Viral Immunology Section, Neuroimmunology Branch
10 Center for Comparative Medicine and California National Primate Research Center

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.

Domaines: Virologie

Shari N Gordon, Anna R Weissman, Valentina Cecchinato, Claudio Fenizia, Zhong-Min Ma, et al.. Preexisting infection with human T-cell lymphotropic virus type 2 neither exacerbates nor attenuates simian immunodeficiency virus SIVmac251 infection in macaques.. Journal of Virology, 2010, 84 (6), pp.3043-58. ⟨10.1128/JVI.01655-09⟩. ⟨pasteur-00589395⟩