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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Gordon, SN; Weissman, AR; Cecchinato, V; Fenizia, C; Ma, Z-M; Lee, T-H; 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

Published Date

  • March 2010

Published In

Volume / Issue

  • 84 / 6

Start / End Page

  • 3043 - 3058

PubMed ID

  • 20071587

Pubmed Central ID

  • PMC2826058

Electronic International Standard Serial Number (EISSN)

  • 1098-5514

Digital Object Identifier (DOI)

  • 10.1128/JVI.01655-09

Language

  • eng

Conference Location

  • United States