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

  • Author(s): 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
  • et al.

Published Web Location

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826058/
No data is associated with this publication.
Abstract

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.

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