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.

Abstract

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.

• Authors: Thomas Musich, Olivia O'Connell, Maria Paz Gonzalez-Perez, Cynthia A Derdeyn, Paul J Peters, Paul R Clapham
• Journal: Retrovirology (Retrovirology) Vol. 12 Pg. 25 (Mar 14 2015) ISSN: 1742-4690 [Electronic] England
• PMID: 25809903 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• env Gene Products, Human Immunodeficiency Virus

Topics

• CD4-Positive T-Lymphocytes (virology)
• Cells, Cultured
• HIV-1 (physiology)
• Humans
• Macrophages (virology)
• Viral Tropism
• Virus Internalization
• env Gene Products, Human Immunodeficiency Virus (metabolism)