Coinfection of Macaques with Simian Immunodeficiency Virus and Simian T Cell Leukemia Virus Type I: Effects on Virus Burdens and Disease Progression

Fultz, Patricia N.; McGinn, Therese M.; Davis, Ian C.; Romano, Joseph; Li, Yuexia

doi:10.1086/314627

Cited by 19 publications

(14 citation statements)

References 62 publications

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“…Similar results have been obtained in a macaque model [13]. Intriguingly, our analysis of HIV-2 RNA load has suggested that suppression of replication of HIV-2 occurs as a consequence of HIV-2/HTLV-I coinfection; thus, the suppression phenomenon may be specific to the less-pathogenic virus of HIV-2.…”

supporting

confidence: 88%

Quantification of Human T‐Lymphotropic Virus Type I (HTLV‐I) Provirus Load in a Rural West African Population: No Enhancement of Human Immunodeficiency Virus Type 2 Pathogenesis, but HTLV‐I Provirus Load Relates to Mortality

et al. 2003

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Human T-lymphotropic virus type I (HTLV-I) provirus load was examined in a cohort of a population in Guinea-Bissau among whom human immunodeficiency virus (HIV) type 2 is endemic. Geometric mean of HIV-2 RNA load among HTLV-I-coinfected subjects was significantly lower than that in subjects infected with HIV-2 alone (212 vs. 724 copies/mL; P=.02). Adjusted for age, sex, and HIV status, the risk of death increased with HTLV-I provirus load; mortality hazard ratio was 1.59 for each log10 increase in HTLV-I provirus copies (P=.038). There is no enhancing effect of HTLV-I coinfection on HIV-2 disease, but high HTLV-I provirus loads may contribute to mortality.

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supporting

confidence: 88%

Quantification of Human T‐Lymphotropic Virus Type I (HTLV‐I) Provirus Load in a Rural West African Population: No Enhancement of Human Immunodeficiency Virus Type 2 Pathogenesis, but HTLV‐I Provirus Load Relates to Mortality

et al. 2003

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“…(6,31,43,56). Repeated exposures to HTLV-2 may induce a more robust infection in the blood of rhesus macaques similar to HTLV-1-and STLV-1-infected animals (21,55). Unlike other coinfection studies with SIV and either HTLV-1 or STLV-1 performed in nonhuman primates, we observed no indication of pathology associated with HTLV-2 infection (21, 55).…”

Section: Cd4mentioning

confidence: 45%

Preexisting Infection with Human T-Cell Lymphotropic Virus Type 2 neither Exacerbates nor Attenuates Simian Immunodeficiency Virus SIV _mac251 Infection in Macaques

Gordon¹,

Weissman²,

Cecchinato³

et al. 2010

J Virol

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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 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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“…Second, the HVS-transformed T-cell lines of these highly susceptible macaques did not contain STLV-1 provirus and yet retained the highly susceptible phenotype. Third, there is considerable precedent in the literature that infection of macaques with STLV-1 or humans with HTLV-1 does not enhance viral load or disease progression associated with SIV or HIV, respectively (13,14). The association between STLV-1 infection and increased susceptibility in vitro and in vivo clearly warrants further prospective studies.…”

Section: Discussionmentioning

confidence: 99%

Intrinsic Susceptibility of Rhesus Macaque Peripheral CD4⁺T Cells to Simian Immunodeficiency Virus In Vitro Is Predictive of In Vivo Viral Replication

Goldstein

Brown

Dehghani

et al. 2000

J Virol

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Previous studies with simian immunodeficiency virus (SIV) infection of rhesus macaques suggested that the intrinsic susceptibility of peripheral blood mononuclear cells (PBMC) to infection with SIV in vitro was predictive of relative viremia after SIV challenge. The present study was conducted to evaluate this parameter in a well-characterized cohort of six rhesus macaques selected for marked differences in susceptibility to SIV infection in vitro. Rank order relative susceptibility of PBMC to SIVsmE543-3-infection in vitro was maintained over a 1-year period of evaluation. Differential susceptibility of different donors was maintained in CD8 ؉ T-cell-depleted PBMC, macrophages, and CD4؉ T-cell lines derived by transformation of PBMC with herpesvirus saimiri, suggesting that this phenomenon is an intrinsic property of CD4 ؉ target cells. Following intravenous infection of these macaques with SIVsmE543-3, we observed a wide range in plasma viremia which followed the same rank order as the relative susceptibility established by in vitro studies. A significant correlation was observed between plasma viremia at 2 and 8 weeks postinoculation and in vitro susceptibility (P < 0.05). The observation that the two most susceptible macaques were seropositive for simian T-lymphotropic virus type 1 may suggests a role for this viral infection in enhancing susceptibility to SIV infection in vitro and in vivo. In summary, intrinsic susceptibility of CD4؉ target cells appears to be an important factor influencing early virus replication patterns in vivo that should be considered in the design and interpretation of vaccine studies using the SIV/macaque model.

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Coinfection of Macaques with Simian Immunodeficiency Virus and Simian T Cell Leukemia Virus Type I: Effects on Virus Burdens and Disease Progression

Cited by 19 publications

References 62 publications

Quantification of Human T‐Lymphotropic Virus Type I (HTLV‐I) Provirus Load in a Rural West African Population: No Enhancement of Human Immunodeficiency Virus Type 2 Pathogenesis, but HTLV‐I Provirus Load Relates to Mortality

Quantification of Human T‐Lymphotropic Virus Type I (HTLV‐I) Provirus Load in a Rural West African Population: No Enhancement of Human Immunodeficiency Virus Type 2 Pathogenesis, but HTLV‐I Provirus Load Relates to Mortality

Preexisting Infection with Human T-Cell Lymphotropic Virus Type 2 neither Exacerbates nor Attenuates Simian Immunodeficiency Virus SIV _mac251 Infection in Macaques

Intrinsic Susceptibility of Rhesus Macaque Peripheral CD4⁺T Cells to Simian Immunodeficiency Virus In Vitro Is Predictive of In Vivo Viral Replication

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Coinfection of Macaques with Simian Immunodeficiency Virus and Simian T Cell Leukemia Virus Type I: Effects on Virus Burdens and Disease Progression

Cited by 19 publications

References 62 publications

Quantification of Human T‐Lymphotropic Virus Type I (HTLV‐I) Provirus Load in a Rural West African Population: No Enhancement of Human Immunodeficiency Virus Type 2 Pathogenesis, but HTLV‐I Provirus Load Relates to Mortality

Quantification of Human T‐Lymphotropic Virus Type I (HTLV‐I) Provirus Load in a Rural West African Population: No Enhancement of Human Immunodeficiency Virus Type 2 Pathogenesis, but HTLV‐I Provirus Load Relates to Mortality

Preexisting Infection with Human T-Cell Lymphotropic Virus Type 2 neither Exacerbates nor Attenuates Simian Immunodeficiency Virus SIV mac251 Infection in Macaques

Intrinsic Susceptibility of Rhesus Macaque Peripheral CD4+T Cells to Simian Immunodeficiency Virus In Vitro Is Predictive of In Vivo Viral Replication

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Preexisting Infection with Human T-Cell Lymphotropic Virus Type 2 neither Exacerbates nor Attenuates Simian Immunodeficiency Virus SIV _mac251 Infection in Macaques

Intrinsic Susceptibility of Rhesus Macaque Peripheral CD4⁺T Cells to Simian Immunodeficiency Virus In Vitro Is Predictive of In Vivo Viral Replication