Journal article

Tissue-Specific Sequence Alterations in the Human Immunodeficiency Virus Type 1 Envelope Favoring CCR5 Usage Contribute to Persistence of Dual-Tropic Virus in the Brain

Lachlan Gray, Michael Roche, Melissa J Churchill, Jasminka Sterjovski, Anne Ellett, Pantelis Poumbourios, Shameem Sheffief, Bin Wang, Nitin Saksena, Damian FJ Purcell, Steven Wesselingh, Anthony L Cunningham, Bruce J Brew, Dana Gabuzda, Paul R Gorry

JOURNAL OF VIROLOGY | AMER SOC MICROBIOLOGY | Published : 2009

Abstract

Most human immunodeficiency virus type 1 (HIV-1) strains isolated from the brain use CCR5 for entry into macrophages and microglia. Strains that use both CCR5 and CXCR4 for entry (R5X4 strains) have been identified in the brains of some individuals, but mechanisms underlying the persistence of R5X4 viruses compartmentalized between the brain and other tissue reservoirs are unknown. Here, we characterized changes in the HIV-1 envelope (Env) that enhance the tropism of R5X4 variants for brain or lymphoid tissue. R5X4 Envs derived from the brains of two individuals had enhanced CCR5 usage in fusion assays compared to R5X4 Envs derived from matched spleen or blood, which was associated with redu..

View full abstract

Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)


Awarded by NIH


Awarded by NATIONAL INSTITUTE OF MENTAL HEALTH


Funding Acknowledgements

We thank J. Sodroski and B. Etemad-Gilbertson for providing Cf2CD4/CCR5 This study was supported in part by project grants from the Australian National Health and Medical Research Council (NHMRC) to P. R. G. (433915) and M. J. C. (433920) and a multicenter program grant from the Australian NHMRC to S. W., A. L. C., and B. J. B. (358399). D. G. was supported by NIH MH83588. J. S. and L. G. were supported by Australian NHMRC Dora Lush Biomedical Research Scholarships. P. R. G. is the recipient of an Australian NHMRC R. Douglas Wright Biomedical Career Development Award.