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Virology. 2017 Aug;508:90-107. doi: 10.1016/j.virol.2017.04.033. Epub 2017 May 15.

Adaptation of HIV-1 to cells with low expression of the CCR5 coreceptor.

Author information

1
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
2
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
3
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA. Electronic address: joseph_sodroski@dfci.harvard.edu.

Abstract

The binding of the human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer ((gp120/gp41)3) to the receptors CD4 and CCR5 triggers virus entry into host cells. To identify Env regions that respond to CCR5 binding, HIV-1 was serially passaged on a CD4-positive canine cell line expressing progressively lower levels of CCR5. HIV-1 replication was observed in cells expressing ~1300 CCR5 molecules/cell. Env changes that conferred this low-CCR5 replication phenotype were located outside of the known CCR5-binding region of the gp120 Env subunit and did not apparently increase CCR5 binding affinity. The adaptation-associated changes, located in the gp120 α1 helix and in the gp41 HR1 heptad repeat and membrane-proximal external region (MPER), enhanced HIV-1 replication in cells at all levels of CCR5 expression. The adapted Envs exhibited a greater propensity to undergo conformational changes, as evidenced by increased exposure of conserved regions near the CD4- and CCR5-binding sites.

KEYWORDS:

CD4; Membrane fusion; Receptor; Trigger; Virus entry

PMID:
28521215
PMCID:
PMC5516540
DOI:
10.1016/j.virol.2017.04.033
[Indexed for MEDLINE]
Free PMC Article

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