Effect of complement consumption by cobra venom factor on the course of primary infection with simian immunodeficiency virus in rhesus monkeys

Cobra venom factor (CVF)-induced consumption of complement proteins was use d to investigate the role of complement in vivo in the immunopathogenesis o f simian immunodeficiency virus of macaques (SIVmac) infection in rhesus mo nkeys. Repeated administration of CVF was shown to deplete complement to <5 % of baseline hemolytic activity of serum complement for 10 days in a norma l monkey. Three groups of SIVmac-infected animals were then evaluated: monk eys treated with CVF resulting in complement depletion from days -1 to 10 p ostinfection, monkeys treated with CVF resulting in complement depletion fr om days 10 to 21 postinfection, and control monkeys that received no CVF. C D8(+) SIVmac-specific cytotoxic T lymphocyte (CTL) generation and CD4(+) T lymphocyte depletion during primary infection were not affected by CVF trea tment. Viral load, assessed by measurements of plasma p27(gag) antigen and viral RNA, was transiently higher during the first 4 weeks following infect ion in the CVF-treated monkeys and the subsequent clinical course in these treated animals was accelerated. These results suggest that complement prot eins may participate in immune defense mechanisms that decrease virus repli cation following the initial burst of intense viremia during primary SIVmac infection. However, we cannot rule out that the observed increased virus r eplication was induced by immune activation resulting fi om the administrat ion of a foreign antigen to these monkeys.