Transgenic dissection of HIV genes involved in lymphoid depletion

Brad T. Tinkle, Hiroyuki Ueda, Lien Ngo, Paul A Luciw, Karen Shaw, Craig A. Rosen, Gilbert Jay

Research output: Contribution to journalArticle

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Abstract

Transgenic mice carrying an HIV provirus, with selective deletion of all three structural genes, developed extensive lymphoid depletion which was detected not only in the spleen and lymph nodes but also in the thymus. Mice with a high level of HIV gene expression developed acute disease which resulted in premature death, and mice with a low level of viral transcripts developed chronic disease with long-term survival. Neither HIV replication nor the envelope glycoprotein (gp120) was required for T cell depletion. Despite abundant viral gene expression early in life, cell death did not become evident until about the time of full lymphoid maturation, suggesting that thymopoiesis was not affected. The more mature T cells in the peripheral lymphoid organs and in the thymic medulla were less sensitive to the apoptotic process than the immature T cells in the thymic cortex. Gradual depletion of the T cell compartment in the peripheral lymphoid organs was intimately accompanied by the reciprocal expansion of the B cell compartment, resulting in the almost complete replacement of T lymphocytes with B immunoblasts in lymph nodes. Unlike T cells, which showed abundant HIV gene expression, B cells did not. The transgenic approach may help identify the HIV nonstructural gene(s) responsible for immune deficiency and help facilitate dissection of its role in inducing apoptosis.

Original languageEnglish (US)
Pages (from-to)32-39
Number of pages8
JournalJournal of Clinical Investigation
Volume100
Issue number1
StatePublished - Jul 1 1997

Fingerprint

Dissection
HIV
T-Lymphocytes
Genes
Gene Expression
B-Lymphocytes
Lymph Nodes
Proviruses
Premature Mortality
Viral Genes
Acute Disease
Thymus Gland
Transgenic Mice
Glycoproteins
Chronic Disease
Cell Death
Spleen
Apoptosis

Keywords

  • Apoptosis
  • B cell expansion
  • HIV genes
  • T cell depletion
  • Trangenic mice

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Tinkle, B. T., Ueda, H., Ngo, L., Luciw, P. A., Shaw, K., Rosen, C. A., & Jay, G. (1997). Transgenic dissection of HIV genes involved in lymphoid depletion. Journal of Clinical Investigation, 100(1), 32-39.

Transgenic dissection of HIV genes involved in lymphoid depletion. / Tinkle, Brad T.; Ueda, Hiroyuki; Ngo, Lien; Luciw, Paul A; Shaw, Karen; Rosen, Craig A.; Jay, Gilbert.

In: Journal of Clinical Investigation, Vol. 100, No. 1, 01.07.1997, p. 32-39.

Research output: Contribution to journalArticle

Tinkle, BT, Ueda, H, Ngo, L, Luciw, PA, Shaw, K, Rosen, CA & Jay, G 1997, 'Transgenic dissection of HIV genes involved in lymphoid depletion', Journal of Clinical Investigation, vol. 100, no. 1, pp. 32-39.
Tinkle BT, Ueda H, Ngo L, Luciw PA, Shaw K, Rosen CA et al. Transgenic dissection of HIV genes involved in lymphoid depletion. Journal of Clinical Investigation. 1997 Jul 1;100(1):32-39.
Tinkle, Brad T. ; Ueda, Hiroyuki ; Ngo, Lien ; Luciw, Paul A ; Shaw, Karen ; Rosen, Craig A. ; Jay, Gilbert. / Transgenic dissection of HIV genes involved in lymphoid depletion. In: Journal of Clinical Investigation. 1997 ; Vol. 100, No. 1. pp. 32-39.
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