Vaccination with Tat toxoid attenuates disease in simian/HIV-challenged macaques

Vaccination with Tat toxoid attenuates disease in simian/HIV-challenged macaques
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DOI:
10.1073/pnas.070049797
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发表时间:
2000-03-28
影响因子:
11.1
通讯作者:
Gallo, RC
Gallo, RC
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Pauza, CD;Trivedi, P;Gallo, RC

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达特蛋白是HIV-1复制所必需的蛋白,可能是HIV-1体内重要的毒力因子。我们用化学灭活的达特环免疫恒河猴,并通过直肠内接种猴/人免疫缺陷病毒89.6PD来研究达特蛋白在病毒致病中的作用。免疫动物的疾病显著减弱,病毒RNA、干扰素α和CD 4(+)T细胞上趋化因子受体(CXCR 4和CCR 5)表达降低;感染的这些特征与达特的体外作用有关,并对感染期间产生的细胞外达特蛋白产生类似的反应。免疫接种达特环抑制病毒发病机制的关键步骤,应包括在治疗或预防HIV-1疫苗。
The Tat protein is essential for HIV type 1 (HIV-1) replication and may be an important virulence factor in vivo, We studied the role of Tat in viral pathogenesis by immunizing rhesus macaques with chemically inactivated Tat toroid and challenging these animals by intrarectal inoculation with the simian/human immunodeficiency virus 89.6PD. Immune animals had significantly attenuated disease with lowered viral RNA, interferon-alpha, and chemokine receptor expression (CXCR4 and CCR5) on CD4(+) T cells; these features of infection have been linked to in vitro effects of Tat and respond similarly to extracellular Tat protein produced during infection. Immunization with Tat toroid inhibits key steps in viral pathogenesis and should be included in therapeutic or preventive HIV-1 vaccines.