Interaction of several complement proteins with gp120 and gp41, the two envelope glycoproteins of HIV-1.
OBJECTIVE
To study the binding of human complement proteins to gp41 and gp120 of HIV-1.


METHODS
The interaction of complement proteins with gp41 and gp120 and their effect on the gp41-gp120 complex in enzyme-linked immunosorbent assays (ELISA) and on stably transfected Schneider-2 cells expressing a gp41-gp120 complex was investigated. The molecular basis of these interactions was analysed by computer-supported sequence analysis.


RESULTS
gp41 strongly binds human complement regulatory proteins factors H and properdin, and weakly binds factors I and B. The binding occurs with recombinant soluble (rs) gp41 fixed on ELISA plates as well as gp41-gp120 complex expressed on Schneider-2 cells. The basis for this binding potential might be an amino-acid (aa) sequence of gp41 displaying homologies to sites in human C3. rgp120 also binds C3(H2O), a C3b-like form of C3, and C4b. These binding features of gp120 can be explained by homology of constant region (CR) 4 in gp120 to sites in C4b binding protein. Additionally, CR1 in gp120 exhibits a weak similarity to human properdin. Preincubation of rsgp41 with either factor H or properdin, and of rgp120 with C3b or C4b affected the interaction between rsgp41 and rgp120. Incubation of Schneider-2 cells, expressing a functional gp41-gp120 complex, with factor H reduced the detectable amount of gp120. This effect was similar to that induced by soluble CD4.


CONCLUSIONS
These results strongly suggest that HIV-1 envelope proteins interact with human complement proteins. Additionally, C3b-like features of gp41 and the C3b/C4b binding structures in gp120 may affect the non-covalent association between gp41 and gp120.
Stoiber
H
H
Ludwig Boltzmann Institute for AIDS Research, University of Innsbruck, Austria.
Ebenbichler
C
C
Schneider
R
R
Janatova
J
J
Dierich
M P
MP
D000595:Amino Acid Sequence; D000818:Animals; D003179:Complement C3b / Q000235:genetics / Q000378:metabolism; D015935:Complement C4b / Q000235:genetics / Q000378:metabolism; D003165:Complement System Proteins / Q000235:genetics / Q000378:metabolism*; D006168:Guinea Pigs; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007127:Immunoglobulin Constant Regions; D008969:Molecular Sequence Data; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D014982:Xenopus laevis
D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D007127:Immunoglobulin Constant Regions; D003179:Complement C3b; D015935:Complement C4b; D003165:Complement System Proteins