Interferon induction by HIV glycoprotein 120: role of the V3 loop
- PMID: 7526537
- DOI: 10.1006/viro.1994.1617
Interferon induction by HIV glycoprotein 120: role of the V3 loop
Abstract
We have studied the mechanism of IFN induction by HIV-1 in peripheral blood mononuclear cells (PBMC), using recombinant viral membrane glycoproteins as potential inducers. Whereas 8 nM HIVIIIB-derived gp120 resulted in IFN levels between 80 and 2000 IU/ml with PBMC from different donors, gp120 from the MN strain was not an inducer. Preincubation of HIVIIIB-gp120 with a monoclonal antibody (mAB) to its CD4 binding domain or of PBMC with a mAB to the gp120 binding domain of CD4 abolished IFN induction. Antibodies against the third extracellular domain of CD4 which did not block binding of gp120, however, were also inhibitory. Furthermore, several mABs to the third variable loop (V3) of HIVIIIB-gp120 also blocked IFN induction, suggesting an important role of V3 in this process. This was further supported by the inhibitory action of peptides homologous to complete or partial sequences of V3. We conclude that after binding of gp120 to its CD4 receptor the V3 loop can be positioned close to the membrane of the responder cells by bending of gp120-occupied CD4 at its hinge region between extracellular domains 2 and 3. As a result V3 is able to interact with a V3-specific "secondary receptor" on the membranes of these cells. We suggest that it is the latter interaction which triggers IFN induction.
Similar articles
-
Binding of antibodies to virion-associated gp120 molecules of primary-like human immunodeficiency virus type 1 (HIV-1) isolates: effect on HIV-1 infection of macrophages and peripheral blood mononuclear cells.Virology. 1997 Mar 17;229(2):360-9. doi: 10.1006/viro.1997.8443. Virology. 1997. PMID: 9126249
-
The effect of low-profile serine substitutions in the V3 loop of HIV-1 gp120 IIIB/LAI on the immunogenicity of the envelope protein.Virology. 1998 Nov 10;251(1):59-70. doi: 10.1006/viro.1998.9392. Virology. 1998. PMID: 9813203
-
Cooperation of the V1/V2 and V3 domains of human immunodeficiency virus type 1 gp120 for interaction with the CXCR4 receptor.J Virol. 2001 Jun;75(12):5457-64. doi: 10.1128/JVI.75.12.5457-5464.2001. J Virol. 2001. PMID: 11356952 Free PMC article.
-
Identification of a new neutralizing epitope conformationally affected by the attachment of CD4 to gp120.J Immunol. 1993 Jul 1;151(1):449-57. J Immunol. 1993. PMID: 7686944
-
The role of the V3 loop of gp120 in HIV infection.AIDS. 1991;5 Suppl 2:S21-33. doi: 10.1097/00002030-199101001-00004. AIDS. 1991. PMID: 1845049 Review. No abstract available.
Cited by
-
Toll-like receptor 3 agonist poly(I:C)-induced antiviral response in human corneal epithelial cells.Immunology. 2006 Jan;117(1):11-21. doi: 10.1111/j.1365-2567.2005.02258.x. Immunology. 2006. PMID: 16423036 Free PMC article.
-
Pepscan mapping of viral hemorrhagic septicemia virus glycoprotein G major lineal determinants implicated in triggering host cell antiviral responses mediated by type I interferon.J Virol. 2010 Jul;84(14):7140-50. doi: 10.1128/JVI.00023-10. Epub 2010 May 12. J Virol. 2010. PMID: 20463070 Free PMC article.
-
The role of type I interferon production by dendritic cells in host defense.Biochimie. 2007 Jun-Jul;89(6-7):843-55. doi: 10.1016/j.biochi.2007.04.018. Epub 2007 May 8. Biochimie. 2007. PMID: 17544561 Free PMC article. Review.
-
Human cytomegalovirus elicits a coordinated cellular antiviral response via envelope glycoprotein B.J Virol. 2004 Feb;78(3):1202-11. doi: 10.1128/jvi.78.3.1202-1211.2004. J Virol. 2004. PMID: 14722275 Free PMC article.
-
Molecular pathways in virus-induced cytokine production.Microbiol Mol Biol Rev. 2001 Mar;65(1):131-50. doi: 10.1128/MMBR.65.1.131-150.2001. Microbiol Mol Biol Rev. 2001. PMID: 11238989 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
