Human immunodeficiency virus (HIV)-infected cells and free virus directly activate the classical complement pathway in rabbit, mouse and guinea-pig sera; activation results in virus neutralization by virolysis.
Since animal models of human immunodeficiency virus (HIV) infection are being used increasingly in determining various aspects of virus/host interaction and as models for virus expression, it will be important to assess any significant differences in anti-viral immune responses between animals and humans. Previous studies have shown that incubation of HIV with non-immune sera from several animal species results in virus neutralization, and that rabbit serum can lyse HIV-infected cells. The objectives of the current study were to evaluate the animal complement pathway(s) activated by HIV and HIV-infected cells and determine the mechanism by which complement could mediate viral neutralization. Incubation of HIV-infected cells with mouse, guinea-pig or rabbit sera resulted in cell-surface deposition of C3 fragments. Deposition of C3 fragments did not occur either in the presence of C4-deficient guinea-pig serum or in the absence of Ca2+, indicating that activation by infected cells occurred via the classical pathway. Neutralization of free virus was also mediated by the classical pathway since C4-deficient guinea-pig serum and Ca(2+)-chelated sera lacked activity. Serum treatment of virus resulted in release of HIV reverse transcriptase (RT), suggesting that neutralization occurred by C5b-9-mediated virolysis. RT was also released from simian immunodeficiency virus by animal complement. Antibodies in animal sera were not responsible for the classical pathway activation by free virus or HIV-infected cells. These results define several substantial differences between animal and human complement reactivity with HIV which could significantly affect the ability of HIV to replicate in animals, and which need to be considered in the assessment of animal models of HIV infection.
Department of Immunology and Microbiology, Rush-Presbyterian-St Luke's Medical Center, Chicago, Illinois 60612.
G T
GT
Spear
B L
BL
Sullivan
D M
DM
Takefman
A L
AL
Landay
T F
TF
Lint
D000818:Animals; D002478:Cells, Cultured; D003171:Complement Pathway, Classical / Q000276:immunology*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006678:HIV / Q000276:immunology* / Q000502:physiology; D015658:HIV Infections / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D013045:Species Specificity; D014779:Virus Replication / Q000276:immunology