Hladik Florian, Sakchalathorn Polachai, Ballweber Lamar, Lentz Gretchen, Fialkow Michael, Eschenbach David, McElrath M Juliana
Program in Infectious Diseases, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Immunity. 2007 Feb;26(2):257-70. doi: 10.1016/j.immuni.2007.01.007.
Understanding the initial events in the establishment of vaginal human immunodeficiency virus type-1 (HIV-1) entry and infection has been hampered by the lack of appropriate experimental models. Here, we show in an ex vivo human organ culture system that upon contact in situ, HIV-1 rapidly penetrated both intraepithelial vaginal Langerhans and CD4(+) T cells. HIV-1 entered CD4(+) T cells almost exclusively by CD4 and CCR5 receptor-mediated direct fusion, without requiring passage from Langerhans cells, and overt productive infection ensued. By contrast, HIV-1 entered CD1a(+) Langerhans cells primarily by endocytosis, by means of multiple receptors, and virions persisted intact within the cytoplasm for several days. Our findings shed light on the very earliest steps of mucosal HIV infection in vivo and may guide the design of effective strategies to block local transmission and prevent HIV-1 spread.
由于缺乏合适的实验模型，对阴道人免疫缺陷病毒1型（HIV-1）进入和感染建立过程中初始事件的理解一直受到阻碍。在此，我们在体外人体器官培养系统中表明，原位接触时，HIV-1能迅速穿透阴道上皮内的朗格汉斯细胞和CD4(+) T细胞。HIV-1几乎完全通过CD4和CCR5受体介导的直接融合进入CD4(+) T细胞，无需从朗格汉斯细胞传递，随后发生明显的 productive 感染。相比之下，HIV-1主要通过内吞作用，借助多种受体进入CD1a(+) 朗格汉斯细胞，病毒粒子在细胞质内完整存留数天。我们的研究结果揭示了体内黏膜HIV感染的最初步骤，可能为设计有效的策略以阻断局部传播和预防HIV-1扩散提供指导。 （注：productive这个词在医学语境里可能有特定含义，这里直接保留英文未翻译，因为不太明确准确的中文表述，需结合更专业的医学知识来确定最合适的翻译。）
