title: Soluble gC1q-R/p33, a cell protein that binds to the globular "heads" of C1q, effectively inhibits the growth of HIV-1 strains in cell cultures.
abstract: C1q and the outer envelope protein of HIV, gp120, have several structural and functional similarities. Therefore, it is plausible to assume that proteins that are able to interact with C1q may also interact with isolated gp120 as well as the whole HIV-1 virus. Based on this hypothesis, we studied the potential ability of the recombinant form of the 33-kDa protein, which binds to the globular "heads" of C1q (gC1q-R/p33), to inhibit the growth of different HIV-1 strains in cell cultures. gC1q-R/p33 was found to effectively and dose-dependently inhibit the production of one T-lymphotropic (X4) and one macrophage-tropic (R5) strain in human T cell lines (MT-4 and H9) and human monocyte-derived macrophage cultures, respectively. At a concentration range of 5-25 microg/ml, gC1q-R caused a marked and prolonged suppression of virus production. The extent of inhibition was enhanced when gC1q-R was first incubated with and then removed from the target cell cultures before virus infection, compared to that when the cells were infected with gC1q-R-HIV mixtures. The extent of inhibition was comparable to that of the Leu3a anti-CD4 antibody. Addition of gC1q-R to the cell cultures on day 1 or 2 after infection induced markedly less inhibition of HIV-1 growth than pretreatment of the cells just before or together with the infective HIV strains. In ELISA experiments, gC1q-R did not bind to a solid-phase recombinant gp120 while strong and dose-dependent binding of gC1q-R to solid-phase CD4 was observed. Our present findings indicate that gC1q-R is an effective inhibitor of HIV-1 infection, which prevents viral entry by blocking the interaction between CD4 and gp120. Since gC1q-R is a human protein, it is most probably not antigenic in humans. It would seem logical, therefore, to consider gC1q-R or its fragments involved in the CD4 binding as potential therapeutic agents.
authors.affiliation: Institute of Microbiology, University Medical School, Debrecen, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Szabó
authors.forename: L
authors.initials: L
authors.lastname: Cervenák
authors.forename: F D
authors.initials: FD
authors.lastname: Tóth
authors.forename: Z
authors.initials: Z
authors.lastname: Prohászka
authors.forename: L
authors.initials: L
authors.lastname: Horváth
authors.forename: K
authors.initials: K
authors.lastname: Kerekes
authors.forename: Z
authors.initials: Z
authors.lastname: Beck
authors.forename: A
authors.initials: A
authors.lastname: Bácsi
authors.forename: A
authors.initials: A
authors.lastname: Erdei
authors.forename: E I
authors.initials: EI
authors.lastname: Peerschke
authors.forename: G
authors.initials: G
authors.lastname: Füst
authors.forename: B
authors.initials: B
authors.lastname: Ghebrehiwet
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism; D002352:Carrier Proteins; D002460:Cell Line; D015922:Complement C1q / Q000737:chemistry / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D018960:Hyaluronan Receptors; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000821:virology; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement / Q000008:administration & dosage* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012995:Solubility; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; C087299:C1QBP protein, human; D015704:CD4 Antigens; D002352:Carrier Proteins; D015699:HIV Envelope Protein gp120; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; D011994:Recombinant Proteins; C032402:complement 1q receptor; D015922:Complement C1q