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Open Access Publications from the University of California

Preexisting infection with human T-cell lymphotropic virus type 2 neither exacerbates nor attenuates simian immunodeficiency virus SIVmac251infection in macaques

  • Author(s): Gordon, SN
  • Weissman, AR
  • Cecchinato, V
  • Fenizia, C
  • Ma, ZM
  • Lee, TH
  • Zaffiri, L
  • Andresen, V
  • Parks, RW
  • Jones, KS
  • Heraud, JM
  • Ferrari, MG
  • Chung, HK
  • Venzon, D
  • Mahieux, R
  • Murphy, EL
  • Jacobson, S
  • Miller, CJ
  • Ruscetti, FW
  • Franchini, G
  • et al.

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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 SIVmac251-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 SIVmac251demonstrated comparable levels of SIVmac251viral 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/SIVmac251coinfected animals versus SIVmac251singly infected controls. Thus, HTLV-2 targets mucosal sites, persists, and importantly does not exacerbate SIVmac251infection. 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/SIVmac251infection. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

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