Title

Exclusive and Persistent Use of the Entry Coreceptor CXCR4 by Human Immunodeficiency Virus Type 1 from a Subject Homozygous for CCR5 Δ32

Authors

Nelson L. Michael, Naval Medical Research Institute at Bethesda
Julie A. E. Nelson, University of North Carolina at Chapel Hill
Vineet N. Kewalramani, New York University Medical Center
George Chang, Naval Medical Research Institute at Bethesda
Stephen J. O'Brien, National Cancer Institute at RockvilleFollow
John R. Mascola, Naval Medical Research Institute at Bethesda
Barbara Volsky, Naval Medical Research Institute at Bethesda
Mark Louder, Naval Medical Research Institute at Bethesda
Gilbert C. White II, University of North Carolina at Chapel Hill
Dan R. Littman, New York University Medical Center
Ronald Swanstrom, University of North Carolina at Chapel Hill
Thomas R. O'Brien, National Cancer Institute at Rockville

Document Type

Article

Publication Date

7-1998

Publication Title

Journal of Virology

ISSN

0022-538X

Volume

72

Issue/No.

7

First Page

6040

Last Page

6047

Abstract

Individuals who are homozygous for the 32-bp deletion in the gene coding for the chemokine receptor and major human immunodeficiency virus type 1 (HIV-1) coreceptor CCR5 (CCR5 −/−) lack functional cell surface CCR5 molecules and are relatively resistant to HIV-1 infection. HIV-1 infection in CCR5 −/− individuals, although rare, has been increasingly documented. We now report that the viral quasispecies from one such individual throughout disease is homogenous, T cell line tropic, and phenotypically syncytium inducing (SI); exclusively uses CXCR4; and replicates well in CCR5−/− primary T cells. The recently discovered coreceptors BOB and Bonzo are not used. Although early and persistent SI variants have been described in longitudinal studies, this is the first demonstration of exclusive and persistent CXCR4 usage. With the caveat that the earliest viruses available from this subject were from approximately 4 years following primary infection, these data suggest that HIV-1 infection can be mediated and persistently maintained by viruses which exclusively utilize CXCR4. The lack of evolution toward the available minor coreceptors in this subject underscores the dominant biological roles of the major coreceptors CCR5 and CXCR4. This and two similar subjects (R. Biti, R. Ffrench, J. Young, B. Bennetts, G. Stewart, and T. Liang, Nat. Med. 3:252–253, 1997; I. Theodoreu, L. Meyer, M. Magierowska, C. Katlama, and C. Rouzioux, Lancet 349:1219–1220, 1997) showed relatively rapid CD4⁺ T-cell declines despite average or low initial viral RNA load. Since viruses which use CXCR4 exclusively cannot infect macrophages, these data have implications for the relative infection of the T-cell compartment versus the macrophage compartment in vivo and for the development of CCR5-based therapeutics.

Comments

©1998, American Society for Microbiology

Additional Comments

National Cancer Institute contract #: NO1-CP-85649' US Army contract #s: DAMD17-94-J-4430, DAMD17-93-V-3004; National Cancer Institute training grant #: T32-CA-09156

NSUWorks Citation

Michael, Nelson L.; Julie A. E. Nelson; Vineet N. Kewalramani; George Chang; Stephen J. O'Brien; John R. Mascola; Barbara Volsky; Mark Louder; Gilbert C. White II; Dan R. Littman; Ronald Swanstrom; and Thomas R. O'Brien. 1998. "Exclusive and Persistent Use of the Entry Coreceptor CXCR4 by Human Immunodeficiency Virus Type 1 from a Subject Homozygous for CCR5 Δ32." Journal of Virology 72, (7): 6040-6047. https://nsuworks.nova.edu/cnso_bio_facarticles/671

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015