HIV-1 non-macrophage-tropic R5 envelope glycoproteins are not more tropic for entry into primary CD4+ T-cells than envelopes highly adapted for macrophages
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- 作者：Thomas Musich ; Olivia O’Connell ; Maria Paz Gonzalez-Perez…
- 关键词：HIV ; 1 ; Tropism ; Macrophage ; tropism ; Non ; macrophage ; tropism ; Dendritic cells ; Trans ; infection ; Envelope ; T ; cells ; Macrophages ; Functionality
- 刊名：Retrovirology
- 出版年：2015
- 出版时间：December 2015
- 年：2015
- 卷：12
- 期：1
- 全文大小：578 KB
- 参考文献：1. Berger, EA, Doms, RW, Fenyo, E-M, Korber, BTM, Littman, DR, Moore, JP (1998) A new classification for HIV-1. Nature 391: pp. 240 rnal" href="http://dx.doi.org/10.1038/34571" target="_blank" title="It opens in new window">CrossRef
- 刊物主题：Virology; Infectious Diseases; Cancer Research;
- 出版者：BioMed Central
- ISSN：1742-4690
文摘
Background Non-mac-tropic HIV-1 R5 viruses are predominantly transmitted and persist in immune tissue even in AIDS patients who carry highly mac-tropic variants in the brain. Non-mac-tropic R5 envelopes (Envs) require high CD4 levels for infection contrasting with highly mac-tropic Envs, which interact more efficiently with CD4 and mediate infection of macrophages that express low CD4. Non-mac-tropic R5 Envs predominantly target T-cells during transmission and in immune tissue where they must outcompete mac-tropic variants. Here, we investigated whether Env+ pseudoviruses bearing transmitted/founder (T/F), early and late disease non-mac-tropic R5 envelopes mediated more efficient infection of CD4+ T-cells compared to those with highly mac-tropic Envs. Results Highly mac-tropic Envs mediated highest infectivity for primary T-cells, Jurkat/CCR5 cells, myeloid dendritic cells, macrophages, and HeLa TZM-bl cells, although this was most dramatic on macrophages. Infection of primary T-cells mediated by all Envs was low. However, infection of T-cells was greatly enhanced by increasing virus attachment with DEAE dextran and spinoculation, which enhanced the three Env+?virus groups to similar extents. Dendritic cell capture of viruses and trans-infection also greatly enhanced infection of primary T-cells. In trans-infection assays, non-mac-tropic R5 Envs were preferentially enhanced and those from late disease mediated levels of T-cell infection that were equivalent to those mediated by mac-tropic Envs. Conclusions Our results demonstrate that T/F, early or late disease non-mac-tropic R5 Envs do not preferentially mediate infection of primary CD4+ T-cells compared to highly mac-tropic Envs from brain tissue. We conclude that non-macrophage-tropism of HIV-1 R5 Envs in vitro is determined predominantly by a reduced capacity to target myeloid cells via low CD4 rather than a specific adaptation for T-cells entry that precludes macrophage infection.