TRANSGENIC DISSECTION OF HIV GENES INVOLVED IN LYMPHOID DEPLETION

Transgenic mice carrying an HIV provirus, with selective deletion of a ll three structural genes, developed extensive lymphoid depletion whic h 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 o f viral transcripts del eloped chronic disease with longterm survival, Neither HIV replication nor the envelope glycoprotein (gp120) was req uired for T cell depletion, Despite abundant viral gene expression ear ly in life, cell death did not become evident until about the time of full lymphoid maturation, suggesting that thymopoiesis was not affecte d, The more mature T cells in the peripheral lymphoid organs and in th e thymic medulla were less sensitive to the apoptotic process than the immature T cells in the thymic cortex, Gradual depletion of the T cel l compartment in the peripheral lymphoid organs was intimately accompa nied by the reciprocal expansion of the B cell compartment, resulting in the almost complete replacement of T lymphocytes with B immunoblast s in lymph nodes, Unlike T cells, which showed abundant HIV gene expre ssion, B cells did not, The transgenic approach may help identify the HIV nonstructural gene(s) responsible for immune deficiency and help f acilitate dissection of its role in inducing apoptosis.