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题目:: Mode of transmission affects the sensitivity of human immunodeficiency virus type 1 to restriction by rhesus TRIM5alpha.
作者:: Richardson(Max W),Carroll(Richard G),Stremlau(Matthew),Korokhov(Nikolay),Humeau(Laurent M),Silvestri(Guido),Sodroski(Joseph),Riley(James L)
状态:: 发布时间2008-10-27 , 更新时间 2016-10-19
期刊:: J Virol
摘要:: Rhesus TRIM5alpha (rhTRIM5alpha), but not human TRIM5alpha (huTRIM5alpha), potently inhibits human immunodeficiency virus (HIV) infection and is thus a potentially valuable therapeutic tool. Primary human CD4 T cells engineered to express rhTRIM5alpha were highly resistant to cell-free HIV type 1 (HIV-1) infection. However, when cocultured with unmodified T cells, rhTRIM5alpha-expressing cells became highly permissive to HIV-1 infection. Physical separation of rhTRIM5alpha-expressing cells and unmodified cells revealed that rhTRIM5alpha efficiently restricts cell-free but not cell-associated HIV transmission. Furthermore, we observed that HIV-infected human cells could infect rhesus CD4 T cells by cell-to-cell contact, but the infection was self-limiting. Subsequently, we noted that a spreading infection ensued when HIV-1-infected rhTRIM5alpha-expressing human cells were cultured with huTRIM5alpha- but not rhTRIM5alpha-expressing cells. Our results suggest that cell-associated HIV transmission in humans is blocked only when both donor and recipient cells express rhTRIM5alpha. These studies further define the role of rhTRIM5alpha in cell-free and cell-associated HIV transmission and delineate the utility of rhTRIM5alpha in anti-HIV therapy.
语言:: eng
DOI:

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