Bioinformatic analysis of neurotropic HIV envelope sequences identifies polymorphisms in the gp120 bridging sheet that increase macrophage-tropism through enhanced interactions with CCR5

Virology
Megan E MeffordD Gabuzda

Abstract

Macrophages express low levels of the CD4 receptor compared to T-cells. Macrophage-tropic HIV strains replicating in brain of untreated patients with HIV-associated dementia (HAD) express Envs that are adapted to overcome this restriction through mechanisms that are poorly understood. Here, bioinformatic analysis of env sequence datasets together with functional studies identified polymorphisms in the β3 strand of the HIV gp120 bridging sheet that increase M-tropism. D197, which results in loss of an N-glycan located near the HIV Env trimer apex, was detected in brain in some HAD patients, while position 200 was estimated to be under positive selection. D197 and T/V200 increased fusion and infection of cells expressing low CD4 by enhancing gp120 binding to CCR5. These results identify polymorphisms in the HIV gp120 bridging sheet that overcome the restriction to macrophage infection imposed by low CD4 through enhanced gp120-CCR5 interactions, thereby promoting infection of brain and other macrophage-rich tissues.

References

May 13, 1999·Proceedings of the National Academy of Sciences of the United States of America·M BabaM Fujino
Jun 25, 1999·AIDS Research and Human Retroviruses·P ShapshakK Goodkin
Nov 9, 2000·Genes & Development·R W Doms, D Trono
Nov 22, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jacqueline D ReevesRobert W Doms
Mar 31, 2004·Proceedings of the National Academy of Sciences of the United States of America·Zhihai SiJoseph G Sodroski
Aug 26, 2004·Virology·Bridget A PufferRobert W Doms
Jan 11, 2005·Current HIV Research·Paul R GorryDana Gabuzda
Feb 25, 2005·Nature·Bing ChenStephen C Harrison
Jun 23, 2006·PLoS Computational Biology·Sergei L Kosakovsky PondAndrew J Leigh Brown
Jul 18, 2006·Current HIV Research·Rebecca DunfeeDana Gabuzda
Oct 4, 2006·Proceedings of the National Academy of Sciences of the United States of America·Rebecca L DunfeeDana Gabuzda
Jan 24, 2007·PLoS Computational Biology·Art F Y PoonSimon D W Frost
Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Paul J PetersPaul R Clapham
Feb 5, 2008·Retrovirology·Andrew I Dayton

❮ Previous
Next ❯

Citations

Mar 11, 2016·Cell Host & Microbe·Quentin J Sattentau, Mario Stevenson
Oct 17, 2019·Frontiers in Immunology·Kirstie Melissa BertramAndrew Nicholas Harman
Apr 18, 2020·Proceedings of the National Academy of Sciences of the United States of America·Viviane M AndradeMario Stevenson
Oct 20, 2020·Frontiers in Immunology·Alexander OschwaldDaniel Erny

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Antigenic Modulation

Antigenic modulation occurs when an antibody cross-links antigens on a cell surface, causing the antigens to become internalized. This can lead to therapeutic failure of monoclonal antibodies as the expression of the antigen becomes decreased on target cells. Find the latest research on antigenic modulation here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.