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

Retrovirology

Paul R Clapham¹  Paul J Peters²  Cynthia A Derdeyn³  Maria Paz Gonzalez-Perez²  Olivia O’Connell²  Thomas Musich² 

[1] Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, 55 N. Lake Ave, Worcester 01655, MA, USA;Program in Molecular Medicine, University of Massachusetts Medical School, 373, Plantation Street, Worcester 01605, MA, USA;Department of Pathology and Laboratory Medicine, Emory Vaccine Center at Yerkes National Primate Center, Emory University, 954 Gatewood Road, Atlanta 30329, GA, USA

关键词: Functionality;    Macrophages;    T-cells;    Envelope;    Trans-infection;    Dendritic cells;    Non-macrophage-tropism;    Macrophage-tropism;    Tropism;    HIV-1;   

Others  :  1162826
DOI  :  10.1186/s12977-015-0141-0

 received in 2014-10-15, accepted in 2015-01-15,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Musich et al.; licensee BioMed Central.

【 图 表 】

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