CCR5- and CXCR4-utilizing strains of human immunodeficiency virus type 1 exhibit differential tropism and pathogenesis in vivo

Robert D. Berkowitz, Sabina Alexander, Cris Bare, Valerie Linquist-Stepps, Mark Bogan, Mary E. Moreno, Lisa Gibson, Eric Wieder, Jon Kosek, Cheryl A. Stoddart, Joseph M. Mccune

Research output: Contribution to journalArticle

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Abstract

CCR5-utilizing (RS) 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.

Original languageEnglish
Pages (from-to)10108-10117
Number of pages10
JournalJournal of Virology
Volume72
Issue number12
StatePublished - Dec 1 1998
Externally publishedYes

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tropisms
Tropism
Human immunodeficiency virus 1
HIV-1
Thymocytes
thymocytes
pathogenesis
Infection
Stromal Cells
infection
stromal cells
Thymus Gland
Macrophages
cortex
macrophages
mice
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Berkowitz, R. D., Alexander, S., Bare, C., Linquist-Stepps, V., Bogan, M., Moreno, M. E., ... Mccune, J. M. (1998). CCR5- and CXCR4-utilizing strains of human immunodeficiency virus type 1 exhibit differential tropism and pathogenesis in vivo. Journal of Virology, 72(12), 10108-10117.

CCR5- and CXCR4-utilizing strains of human immunodeficiency virus type 1 exhibit differential tropism and pathogenesis in vivo. / Berkowitz, Robert D.; Alexander, Sabina; Bare, Cris; Linquist-Stepps, Valerie; Bogan, Mark; Moreno, Mary E.; Gibson, Lisa; Wieder, Eric; Kosek, Jon; Stoddart, Cheryl A.; Mccune, Joseph M.

In: Journal of Virology, Vol. 72, No. 12, 01.12.1998, p. 10108-10117.

Research output: Contribution to journalArticle

Berkowitz, RD, Alexander, S, Bare, C, Linquist-Stepps, V, Bogan, M, Moreno, ME, Gibson, L, Wieder, E, Kosek, J, Stoddart, CA & Mccune, JM 1998, 'CCR5- and CXCR4-utilizing strains of human immunodeficiency virus type 1 exhibit differential tropism and pathogenesis in vivo', Journal of Virology, vol. 72, no. 12, pp. 10108-10117.
Berkowitz RD, Alexander S, Bare C, Linquist-Stepps V, Bogan M, Moreno ME et al. CCR5- and CXCR4-utilizing strains of human immunodeficiency virus type 1 exhibit differential tropism and pathogenesis in vivo. Journal of Virology. 1998 Dec 1;72(12):10108-10117.
Berkowitz, Robert D. ; Alexander, Sabina ; Bare, Cris ; Linquist-Stepps, Valerie ; Bogan, Mark ; Moreno, Mary E. ; Gibson, Lisa ; Wieder, Eric ; Kosek, Jon ; Stoddart, Cheryl A. ; Mccune, Joseph M. / CCR5- and CXCR4-utilizing strains of human immunodeficiency virus type 1 exhibit differential tropism and pathogenesis in vivo. In: Journal of Virology. 1998 ; Vol. 72, No. 12. pp. 10108-10117.
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