title: HIV-1 gp41 and type I interferon: sequence homology and biological as well as clinical implications.
abstract: HIV-1 gp41-like human type I interferon (IFN) could inhibit lymphocyte proliferation and up-modulate MHC class I and II and ICAM-1 molecule expression. Sequence comparison indicates that a similar epitope RILAV-YLKD exists between N-domain of gp41 and two regions in IFN-alpha(aa29-35 and 113-129), IFN-beta (aa31-37 and 125-138) and IFN-omega (aa29-35 and 123-136), which was shown to form IFN-alpha/beta-receptor binding site. Weak sequence similarity was also found to exist in both regions on gp41 and type I IFN of murine and bovine. Experimental studies indicated that a common immunological epitope exists between gp41 and IFN-alpha and -beta. Antibodies against human IFN-alpha and -beta recognized the common immunological epitope and inhibited gp41-binding to the potential cellular receptor protein p45. Moreover, the polyclonal antibody to IFN-beta completely inhibited gp41-binding to human T, B cells and monocytic cells, while IFN-alpha could only inhibit this binding incompletely. It was interestingly observed that human IFN-beta after preincubating with cells could incompletely inhibit the binding of gp41 to human B cells and monocytic cells, and very weakly inhibit the binding to human T cells, indicating that the receptor for IFN-beta-binding may be involved in gp41 binding. This potential relationship may be based on the amino acid sequence homology in the receptor binding region between gp41 and IFN-beta. It was observed that the increased levels of antibodies against human IFN-alpha and -beta exist in HIV-1-infected individuals and are associated with the common epitope on gp41. Besides, several studies provided experimental evidence that the common immunological epitope could induce protective activity against HIV-1. The IFN-alpha-based vaccine has showed a significant reduction of disease progression in IFN-alpha-vaccine-treated HIV-infected patients. Recent experimental evidence indicates that gp41 and IFN-beta were involved in downregulation of CCR5 expression and induction of cell activation or signal transduction. Whether it may be performed by a similar mechanism is still to be investigated.
authors.affiliation: Laboratory of Immunology, Research Centre of Medical Research and School of Life Science and Engineering, Tsinghua University, Beijing, PR China.
authors.forename: Y H
authors.initials: YH
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Xiao
authors.forename: M P
authors.initials: MP
authors.lastname: Dierich
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001665:Binding Sites / Q000235:genetics; D002417:Cattle; D000939:Epitopes / Q000235:genetics; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D019713:Receptors, CCR5 / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000939:Epitopes; D015700:HIV Envelope Protein gp41; D007370:Interferon Type I; D019713:Receptors, CCR5