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

Shari N. Gordon, Anna R. Weissman, Valentina Cecchinato, Claudio Fenizia, Zhong Min Ma, Tzong Hae Lee, Lorenzo Zaffiri, Vibeke Andresen, Robyn Washington Parks, Kathryn S. Jones, Jean Michel Heraud, Maria Grazia Ferrari, Hye Kyung Chung, David Venzon, Renaud Mahieux, Edward L. Murphy, Steven Jacobson, Chris J Miller, Francis W. Ruscetti, Genoveffa Franchini

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 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 SIVmac251 demonstrated comparable levels of SIVmac251 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/SIVmac251 coinfected animals versus SIVmac251 singly infected controls. Thus, HTLV-2 targets mucosal sites, persists, and importantly does not exacerbate SIVmac251 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/SIVmac251 infection.

Original languageEnglish (US)
Pages (from-to)3043-3058
Number of pages16
JournalJournal of Virology
Volume84
Issue number6
DOIs
StatePublished - Mar 2010

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Human T-lymphotropic virus 2
Simian immunodeficiency virus
Simian Immunodeficiency Virus
Macaca
Virus Diseases
T-lymphocytes
T-Lymphocytes
viruses
Infection
infection
Human immunodeficiency virus 1
HIV-1
Coinfection
mixed infection
proviruses
mucosal immunity
Proviruses
Mucosal Immunity
Lymphoid Tissue

ASJC Scopus subject areas

  • Immunology
  • Virology

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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. / 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, Chris J; Ruscetti, Francis W.; Franchini, Genoveffa.

In: Journal of Virology, Vol. 84, No. 6, 03.2010, p. 3043-3058.

Research output: Contribution to journalArticle

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 2010, 'Preexisting infection with human T-cell lymphotropic virus type 2 neither exacerbates nor attenuates simian immunodeficiency virus SIVmac251 infection in macaques', Journal of Virology, vol. 84, no. 6, pp. 3043-3058. https://doi.org/10.1128/JVI.01655-09
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, Chris J ; Ruscetti, Francis W. ; Franchini, Genoveffa. / Preexisting infection with human T-cell lymphotropic virus type 2 neither exacerbates nor attenuates simian immunodeficiency virus SIVmac251 infection in macaques. In: Journal of Virology. 2010 ; Vol. 84, No. 6. pp. 3043-3058.
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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 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 na{\"i}ve macaques to SIVmac251 demonstrated comparable levels of SIVmac251 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/SIVmac251 coinfected animals versus SIVmac251 singly infected controls. Thus, HTLV-2 targets mucosal sites, persists, and importantly does not exacerbate SIVmac251 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/SIVmac251 infection.",
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AU - Fenizia, Claudio

AU - Ma, Zhong Min

AU - Lee, Tzong Hae

AU - Zaffiri, Lorenzo

AU - Andresen, Vibeke

AU - Parks, Robyn Washington

AU - Jones, Kathryn S.

AU - Heraud, Jean Michel

AU - Ferrari, Maria Grazia

AU - Chung, Hye Kyung

AU - Venzon, David

AU - Mahieux, Renaud

AU - Murphy, Edward L.

AU - Jacobson, Steven

AU - Miller, Chris J

AU - Ruscetti, Francis W.

AU - Franchini, Genoveffa

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