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Journal of Virology, December 1998, p. 10108-10117, Vol. 72, No. 12
Gladstone Institute of Virology and
Immunology1 and
Departments of
Microbiology & Immunology and Medicine,
Received 25 June 1998/Accepted 26 August 1998
CCR5-utilizing (R5) and CXCR4-utilizing (X4) strains of human
immunodeficiency virus type 1 (HIV-1) have been studied intensively in
vitro, but the pathologic correlates of such differential tropism in
vivo remain incompletely defined. In this study, X4 and R5 strains of
HIV-1 were compared for tropism and pathogenesis in SCID-hu Thy/Liv
mice, an in vivo model of human thymopoiesis. The X4 strain NL4-3
replicates quickly and extensively in thymocytes in the cortex and
medulla, causing significant depletion. In contrast, the R5 strain Ba-L
initially infects stromal cells including macrophages in the thymic
medulla, without any obvious pathologic consequence. After a period of
3 to 4 weeks, Ba-L infection slowly spreads through the thymocyte
populations, occasionally culminating in thymocyte depletion after week
6 of infection. During the entire time of infection, Ba-L did not
mutate into variants capable of utilizing CXCR4. Therefore, X4 strains
are highly cytopathic after infection of the human thymus. In contrast,
infection with R5 strains of HIV-1 can result in a two-phase process in
vivo, involving apparently nonpathogenic replication in medullary
stromal cells followed by cytopathic replication in thymocytes.
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
CCR5- and CXCR4-Utilizing Strains of Human Immunodeficiency Virus
Type 1 Exhibit Differential Tropism and Pathogenesis In
Vivo
*
Corresponding author. Mailing address: Gladstone
Institute of Virology and Immunology, P.O. Box 419100, San Francisco,
CA 94141-9100. Phone: (415) 695-3828. Fax: (415) 826-8449. E-mail: mike_mccune.givi{at}quickmail.ucsf.edu.
Journal of Virology, December 1998, p. 10108-10117, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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