* Department of Virology, Jerome H. Holland Laboratory,
Rockville, Maryland 20855; Department of Medical Pathology, University of
California, Davis, California 95616; and § Human Genome
Sciences, Inc., Rockville, Maryland 20850
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. (J. Clin. Invest.
1997. 100:32-39.)
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