Infection and pathogenicity of chimeric simian-human immunodeficiency viruses in macaques: Determinants of high virus loads and CD4 cell killing

Chimeric simian-human immunodeficiency viruses (SHIVs) carrying envelope glycoproteins derived from a T cell-macrophage dual-tropic primary isolate (human immunodeficiency virus type 1 [HIV-1] strain DH12) were constructed, When inoculated into macaque monkeys, SHIVMD14 carrying simian immunodeficiency virus-derived nef established significantly higher virus loads than did SHIVMD1, which contains the HIV-1 nef gene, Three patterns of CD4 cell depletion were observed in infected monkeys: exponential and irreversible loss to undetectable levels within 10 weeks of infection; marked reduction during acute infection followed by partial recovery and stabilization (lasting from 10 weeks to >1 year), with a later decline to undetectable levels in some animals; and a transient loss during acute infection, The induced immunodeficiency was accompanied by CD4 cell counts of <50 cells/mu L and was associated with Pneumocystis carinii pneumonia, cytomegalovirus meningoencephalitis, lymphoid depletion, and thymic atrophy.