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15 January 2008

Volume 197, Number 2
The Journal of Infectious Diseases 2008;197:309–318
© 2008 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2008/19702-0021$15.00
DOI: 10.1086/524847
MAJOR ARTICLE

Blood Monocytes Harbor HIV Type 1 Strains with Diversified Phenotypes Including Macrophage‐Specific CCR5 Virus

Younong Xu,1

Haiying Zhu,1

Carrie K. Wilcox,1

Angélique van’t Wout,2,a

Thomas Andrus,1

Nicholas Llewellyn,1

Leonidas Stamatatos,4

James I. Mullins,2

Lawrence Corey,1,3 and

Tuofu Zhu1,3

Departments of 1Laboratory Medicine and 2Microbiology, University of Washington School of Medicine, 3Programs in Infectious Diseases, Fred Hutchinson Cancer Research Center, and 4Seattle Biomedical Research Institute, Seattle, Washington

Background.Recent studies have shown that blood monocytes harbor human immunodeficiency virus type 1 (HIV‐1) variants that are genotypically distinguishable from those in CD4+ T cells. However, the biological function of monocyte‐derived HIV‐1 remains unclear.

Methods.Using pseudovirus assay, we analyzed the phenotype conferred by monocyte‐derived HIV‐1 envelopes from 8 patients.

Results.All pseudoviruses carrying monocyte‐derived HIV‐1 envelopes used CCR5; however, their use of additional coreceptors delineated 4 phenotypes in which viruses used (1) CCR5 only, (2) CCR5 and CXCR4, (3) CCR3 and CCR5, or (4) multiple coreceptors, including CCR1, CCR3, GPR15, CCR5, and CXCR4. More importantly, we observed 2 distinct cell tropism phenotypes for pseudoviruses carrying monocyte‐derived envelopes: (1) monocyte‐derived, macrophage‐specific R5 (MDMS‐R5) virus that, using CCR5 only, could infect monocyte‐derived macrophages (MDMs) but not CD4+ T cells and (2) dual tropic virus that infected both MDMs and primary CD4+ T cells. We found blood monocytes harboring viruses with multiple phenotypes as early as 25 days before seroconversion and as late as 9 years after seroconversion.

Conclusions.These data suggest that HIV‐1 circulating in blood monocytes represents diverse HIV‐1 with multiple phenotypes and that MDMS‐R5 viruses may play an important role in infection with and persistence of HIV‐1 within the monocyte/macrophage lineage.

Received 23 March 2007; accepted 6 July 2007; electronically published 3 January 2008.

Reprints or correspondence: Dr. Tuofu Zhu, Dept. of Laboratory Medicine, Univ. of Washington School of Medicine, Box 358070, 1959 NE Pacific St., Seattle, WA 98195‐8070 ().

Cited by

J. F. Salazar-Gonzalez, M. G. Salazar, B. F. Keele, G. H. Learn, E. E. Giorgi, H. Li, J. M. Decker, S. Wang, J. Baalwa, M. H. Kraus, N. F. Parrish, K. S. Shaw, M. B. Guffey, K. J. Bar, K. L. Davis, C. Ochsenbauer-Jambor, J. C. Kappes, M. S. Saag, M. S. Cohen, J. Mulenga, C. A. Derdeyn, S. Allen, E. Hunter, M. Markowitz, P. Hraber, A. S. Perelson, T. Bhattacharya, B. F. Haynes, B. T. Korber, B. H. Hahn, G. M. Shaw. (2009) Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection. Journal of Experimental Medicine 206:6, 1273-1289
Online publication date: 8-Jul-2009.
CrossRef
Donald E Mosier. (2009) How HIV changes its tropism: evolution and adaptation?. Current Opinion in HIV and AIDS 4:2, 125-130
Online publication date: 1-Apr-2009.
CrossRef

  • Potential conflicts of interest: none reported.

    Presented in part: 12th Conference on Retroviruses and Opportunistic Infections, Boston, 22–25 February 2005 (abstract D118).

    Financial support: Public Health Service (grants AI45402, AI49109, and AI55336 [to T.Z.]); National Institutes of Health (grants R01 HL072631 and P50 HG02360 [to A.v.W.]).

  • Present affiliation: Department of Clinical Viro‐Immunology, Sanquin Research, Plesmanlaan, Amsterdam, The Netherlands.

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