Evidence for the HIV-1 phenotype switch as a causal factor in acquired immunodeficiency
Evidence for the HIV-1 phenotype switch as a causal factor in acquired immunodeficiency
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DOI：
10.1038/nm0398-346
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发表时间：
1998-03-01
期刊：
影响因子：
82.9
通讯作者：
Margolis, LB
中科院分区：
文献类型：
--
作者：
Glushakova, S;Grivel, JC;Margolis, LB
长期感染 HIV-1 后，体内会出现细胞和体液免疫缺陷，但其机制尚不清楚(1)。 HIV-1 的初始感染通过巨噬细胞 (M) 嗜性/非合胞体诱导 (NSI) 病毒 (2,3) 传播，这种病毒会过度激活免疫系统 (4,5)，并且从一种观点来看，会因淋巴组织“耗竭”(4,6) 而导致免疫缺陷。另一种假设是，免疫缺陷是由于 M 向性病毒被 T 细胞 (T) 向性/合胞体诱导 (SI) 病毒取代而引起的，众所周知，这些病毒在体外具有高度细胞病变性，并且在感染个体中在向艾滋病过渡的晚期出现（参考文献 1、7-9）。为了测试这两种可能性，我们开发了一种体液免疫的离体模型，以使用人类淋巴组织来回忆抗原。当离体培养时，该组织支持 M 向性和 T 向性 HIV-1 分离株的有效感染 (10,11)。我们发现，用 M-tropic/NSI HIV-1 分离株对组织进行有效感染可以增强特异性免疫反应，但会被 T-tropic/SI HIV-1 分离株阻断。该机制涉及对 B 细胞活性的特定不可逆影响。我们的结果支持这样的假设：向 T 嗜性病毒的表型转换是 HIV 感染者获得性体液免疫缺陷的关键决定因素。
Both cellular and humoral immunodeficiency develop in vivo after prolonged infection with HIV-1, but the mechanisms are unclear(1). Initial infection with HIV-1 is transmitted by macrophage (M)-tropic/non-syncytia-inducing (NSI) viruses(2,3), which hyperactivate the immune system(4,5), and, in one view, cause immunodeficiency by "exhaustion"(4,6) of lymphoid tissue. An alternative hypothesis is that immunodeficiency is caused by the replacement of M-tropic viruses by T cell (T)-tropic/syncytia-inducing (SI) viruses, which are known to be highly cytopathic in vitro and emerge late in infected individuals around the time of transition to AIDS (refs. 1, 7-9). To test these two possibilities, we have developed an ex vivo model of humoral immunity to recall antigens using human lymphoid tissue. This tissue supports productive infection with both M-and T-tropic HIV-1 isolates when cultured ex vivo(10,11). We found that specific immune responses were enhanced by productive infection of the tissue with M-tropic/NSI HIV-1 isolates, but were blocked by T-tropic/SI HIV-1 isolates. The mechanism involves specific irreversible effect on B-cell activity. Our results support the hypothesis that the phenotype switch to T-tropic viruses is a key determinant of acquired humoral immunodeficiency in patients infected with HIV.