In vitro analysis of complement-dependent HIV-1 cell infection using a model system.
Previous studies based on the use of human serum as a source of C have provided evidence for the C-dependent enhancement of cell infection by HIV-1. The present study was undertaken to distinguish C from other serum factors and to identify the proteins and the mechanisms involved in C-dependent cell infection by HIV-1. The classical C activation pathway was reconstituted from the proteins C1q, C1r, C1s, C4, C2, C3, factor H, and factor I; each were purified to homogeneity. A mixture of these proteins at physiological concentrations was shown to reproduce the ability of normal human serum to enhance the infection of MT2 cells by HIV-1 at low doses of virus. This enhancing effect was abolished when heat-inactivated serum and C2- or C3-depleted serum were used, and was restored upon addition of the corresponding purified proteins. A mixture of two synthetic peptides corresponding to positions 10-15 and 90-97 of human C receptor type 2 (CD21) as well as soluble CD4 both inhibited the C-dependent infection process. These data provide unambiguous evidence that HIV-1 triggers a direct activation of the classical C pathway in vitro and thereby facilitates the infection of MT2 cells at low doses of virus. These findings are consistent with a mechanism involving increased interaction between the virus opsonized by C3b-derived fragment(s) and the CD21 cell receptors and subsequent virus entry through CD4 receptors.
Tacnet-Delorme
P
P
Laboratoire d'Enzymologie Moléculaire, Institut de Biologie Structurale, Grenoble, France.
Boyer
V
V
Thielens
N M
NM
Hernandez
J F
JF
Bally
I
I
Sim
R B
RB
Desgranges
C
C
Arlaud
G J
GJ
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D002460:Cell Line; D003175:Complement C2 / Q000172:deficiency / Q000502:physiology; D003176:Complement C3 / Q000172:deficiency / Q000502:physiology; D003181:Complement C4 / Q000302:isolation & purification / Q000502:physiology; D017242:Complement Factor H / Q000302:isolation & purification / Q000502:physiology; D017244:Complement Factor I / Q000302:isolation & purification / Q000502:physiology; D003165:Complement System Proteins / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018448:Models, Immunological; D017464:Receptors, Complement 3d / Q000737:chemistry / Q000378:metabolism
C493495:CFH protein, human; D003175:Complement C2; D003176:Complement C3; D003181:Complement C4; D017464:Receptors, Complement 3d; D017242:Complement Factor H; D003165:Complement System Proteins; D017244:Complement Factor I