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 language | English (US) |
|---|---|
| Pages (from-to) | 3043-3058 |
| Number of pages | 16 |
| Journal | Journal of Virology |
| Volume | 84 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 2010 |
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ASJC Scopus subject areas
- Immunology
- Virology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Preexisting infection with human T-cell lymphotropic virus type 2 neither exacerbates nor attenuates simian immunodeficiency virus SIVmac251 infection in macaques
AU - Gordon, Shari N.
AU - Weissman, Anna R.
AU - Cecchinato, Valentina
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
PY - 2010/3
Y1 - 2010/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77649089593&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77649089593&partnerID=8YFLogxK
U2 - 10.1128/JVI.01655-09
DO - 10.1128/JVI.01655-09
M3 - Article
C2 - 20071587
AN - SCOPUS:77649089593
VL - 84
SP - 3043
EP - 3058
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 6
ER -