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 used to investigate the role of complement in vivo in the immunopathogenesis of simian immunodeficiency virus of macaques (SIVmac) infection in rhesus monkeys. Repeated administration of CVF was shown to deplete complement to <5% of baseline hemolytic activity of serum complement for 10 days in a normal monkey. Three groups of SIVmac-infected animals were then evaluated: monkeys treated with CVF resulting in complement depletion from days -1 to 10 postinfection, monkeys treated with CVF resulting in complement depletion from days 10 to 21 postinfection, and control monkeys that received no CVF. CD8+ SIVmac-specific cytotoxic T lymphocyte (CTL) generation and CD4+ T lymphocyte depletion during primary infection were not affected by CVF treatment. Viral load, assessed by measurements of plasma p27gag antigen and viral RNA, was transiently higher during the first 4 weeks following infection in the CVF-treated monkeys and the subsequent clinical course in these treated animals was accelerated. These results suggest that complement proteins may participate in immune defense mechanisms that decrease virus replication following the initial burst of intense viremia during primary SIVmac infection. However, we cannot rule out that the observed increased virus replication was induced by immune activation resulting from the administration of a foreign antigen to these monkeys.
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. jschmitz@bidmc.harvard.edu
J E
JE
Schmitz
M A
MA
Lifton
K A
KA
Reimann
D C
DC
Montefiori
L
L
Shen
P
P
Racz
K
K
Tenner-Racz
M W
MW
Ollert
M A
MA
Forman
R S
RS
Gelman
C W
CW
Vogel
N L
NL
Letvin
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003165:Complement System Proteins / Q000187:drug effects*; D004546:Elapid Venoms / Q000008:administration & dosage / Q000494:pharmacology*; D017403:In Situ Hybridization; D008198:Lymph Nodes / Q000821:virology; D018655:Lymphocyte Count; D008253:Macaca mulatta / Q000821:virology*; D012367:RNA, Viral / Q000032:analysis; D012191:Retroviridae Proteins / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification / Q000472:pathogenicity*; D013997:Time Factors; D019562:Viral Load; D014779:Virus Replication
D004546:Elapid Venoms; D012367:RNA, Viral; D012191:Retroviridae Proteins; C040520:avian retrovirus proteins; D003165:Complement System Proteins