Preexisting Infection with Human T-Cell Lymphotropic Virus Type 2 neither Exacerbates nor Attenuates Simian Immunodeficiency Virus SIVmac251 Infection in Macaques
Preexisting Infection with Human T-Cell Lymphotropic Virus Type 2 neither Exacerbates nor Attenuates Simian Immunodeficiency Virus SIVmac251 Infection in Macaques
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DOI：
10.1128/jvi.01655-09
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发表时间：
2010-03-01
影响因子：
5.4
通讯作者：
Franchini, Genoveffa
中科院分区：
文献类型：
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作者：
Gordon, Shari N.;Weissman, Anna R.;Franchini, Genoveffa
据报道，人类t细胞嗜淋巴病毒2型（HTLV-2）和人类免疫缺陷病毒1型（HIV-1）的联合感染要么减缓病程，要么对进展为艾滋病没有影响。在本研究中，我们建立了一个共感染动物模型，研究HTLV-2是否能持续感染猕猴，诱导t细胞反应，并影响猴免疫缺陷病毒sivmac251诱导的疾病。我们发现，将HTLV-2感染的T细胞接种到印度恒河猴体内，可在全身和粘膜部位引发对HTLV-2抗原的体液和T细胞反应。在感染动物的血液、淋巴组织和胃肠道中检测到低水平的HTLV-2原病毒DNA。htlv -2感染的猕猴或幼年猕猴暴露于SIVmac251，显示出SIVmac251病毒复制水平相当，粘膜和外周CD4(+) t细胞损失率相似，t细胞增殖增加。此外，HTLV-2/SIVmac251共感染动物与SIVmac251单独感染对照动物中siv特异性t细胞介导的免疫应答的强度和功能能力均无差异。因此，HTLV-2靶向粘膜部位，持续存在，重要的是不会加重SIVmac251感染。这些数据为开发基于htlv -2的HIV-1减毒载体疫苗提供了动力；这种方法可以引发持续的粘膜免疫，从而预防HIV-1/SIVmac251感染。
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 naive 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.