Journal
IMMUNITY
Volume 26, Issue 2, Pages 257-270Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2007.01.007
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Funding
- NIAID NIH HHS [P30 AI027757, AI35605, K08 AI051980, AI27757, AI51980, R37 AI035605] Funding Source: Medline
- NICHD NIH HHS [HD51455, R01 HD051455] Funding Source: Medline
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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.
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