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Journal of Virology, December 1999, p. 9741-9755, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Persistent CCR5 Utilization and Enhanced Macrophage
Tropism by Primary Blood Human Immunodeficiency Virus Type 1 Isolates
from Advanced Stages of Disease and Comparison to Tissue-Derived
Isolates
Shan
Li,1
Julius
Juarez,1
Mohammed
Alali,1
Dominic
Dwyer,2
Ronald
Collman,3
Anthony
Cunningham,1 and
Hassan M.
Naif1,*
Centre for Virus Research, Westmead
Millennium Institute, National Centre for HIV Virology
Research,1 Department of Virology,
ICPMR,2 Westmead Hospital, University of Sydney,
Westmead, NSW 2145, Australia, and University of Pennsylvania
School of Medicine, Philadelphia, Pennsylvania
19104-60603
Received 7 June 1999/Accepted 26 August 1999
Viral phenotype, tropism, coreceptor usage, and envelope gene
diversity were examined in blood isolates collected from 27 individuals
at different stages of human immunodeficiency virus type 1 (HIV-1)
disease and tissue derived isolates from 10 individuals with AIDS. The
majority (89%) of blood and all tissue HIV-1 isolates from all stages
of infection were non-syncytium inducing and macrophage (M) tropic.
Tropism and productive infection by HIV isolates in both monocytes and
monocyte-derived macrophages (MDM) increased in advanced disease (HIV
tropism for monocytes, 1 of 6 from categories I and II versus 11 of 21 [P = 0.05] from category IV and II [CD4 < 250]; and high-level replication in MDM, 1 of 6 from categories I and
II versus 16 of 21 from categories IV and II [P = 0.015]). There was a high level of replication of blood and tissue
isolates in T lymphocytes without restriction at any stage. Overall,
the level of replication in MDM was 5- to 10-fold greater than in monocytes, with restriction in the latter occurring mainly at entry and
later stages of replication. Only three blood isolates were identified
as syncytium inducing, and all had a dualtropic phenotype. There was a
significant increase of HIV envelope gene diversity, as shown by a
heteroduplex mobility assay, in advanced disease; this may partly
underlie the increase of HIV replication in MDM. Unlike blood isolates
(even those from patients with advanced disease), tissue isolates
displayed greater similarities (90%) in productive infection between
MDM and monocytes. The majority (87%) of all isolates, including those
from patients with advanced disease, used CCR5, and only 5 of 37 isolates showed expanded coreceptor usage. These results indicate that
in the late stage of disease with increasing viral load and diversity,
CCR5 utilization and M-tropism persist in blood and tissue and the
replicative ability in macrophages increases. This suggests that these
characteristics are advantageous to HIV and are important to disease progression.
*
Corresponding author. Mailing address: Molecular
Pathogenesis Laboratory, Centre for Virus Research, Westmead Millennium
Institute, The University of Sydney, Westmead Hospital, NSW 2145, Australia. Phone: (61-2) 9845 6311. Fax: (61-2) 9624 6881. E-mail:
Hassann{at}westgate.wh.usyd.edu.au.
Journal of Virology, December 1999, p. 9741-9755, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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