Summary
A local sequence similarity of HIV envelope proteins (gp120 and gp41) to immunoglobulins suggests that a mimicry phenomenon may form the basis of the HIV-cell membrane interaction and of HIV-induced autoimmune reaction. We explored the hypothesis of any deeper relationship between HIV env proteins and immunoglobulin family members. An overall DNA sequence similarity between gp41 coding region of env gene and the HIV-receptor CD4 gene was observed and a 14-base-long oligonucleotide, almost unique in the GenBank, was found in gp41 and CD4 genes. The alignment of env gene to CD4 gene and to 84 different sequences showed a significantly higher homology score and a nonrandom similarity in the CD4-env alignment. A significant similarity was also found between the env protein and the sequence encoded by an alternate reading frame of CD4 gene. Our observations suggest that gp41 coding region might have a different origin than the gp120 coding region of the env gene, and that a divergent evolution might link gp41 to CD4 or immunoglobulin family members. In this study the analysis of alternate-reading-frame products is also proposed as a novel approach to investigate evolutionary links and structure-function relationships.
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References
Alizon M, Wain-Hobson S, Montagnier L, Sonigo P (1986) Genetic variability of the AIDS virus: nucleotide sequence analysis of two isolates from African patients. Cell 46:63–74
Anand R, Thayer R, Srinivasan A, Nayyar S, Gardner M, Luciw P, Dandekar S (1989) Biological and molecular characterization of human immunodeficiency virus (HIV-1BR) from the brain of a patient with progressive dementia. Virology 168:79–89
Argos P (1989) A possible homology between immunodeficiency virus p24 core protein and picornaviral VP2 coat protein: prediction of HIV p24 antigenic sites. EMBO J 8:779–785
Barker WC, George DG, Hunt L, Garavelli JS (1991) The PIR protein sequence database. Nucleic Acids Res 19:2231–2236 Suppl
Brake DA, Debouck C, Biesecker G (1990) Identification of an Arg-Gly-Asp (RGD) cell adhesion site in human immunodeficiency virus type 1 transactivation protein, tat. J Cell Biol 111:1275–1281
Burks C, Cassidy M, Cinkosky MJ, Cumella KE, Gilna P, Hayden JED, Kee GM, Kelley TA, Kelly M, Kristofferson D, Ryals J (1991) GenBank. Nucleic Acids Res 19:2221–2225 Suppl
Bushman FD, Fujiwara T, Craigie R (1990) Retroviral DNA integration directed by HIV integration protein in vitro. Science 249:1555–1558
Buskila D, Gladman D (1990) Musculoskeletal manifestations of infection with human immunodeficiency virus. Rev Infect Dis 12:223–235
Chee MS, Satchwell SC, Preddie E, Weston KM, Barrell BG (1990) Human cytomegalovirus encodes three G proteincoupled receptor homologues. Nature 344:774–777
Clayton LK, Sieh M, Pious DA, Reinherz EL (1989) Identification of human CD4 residues affecting class II MHC versus HIV-1 gp120 binding. Nature 339:548–551
Dalgleish AG, Beverley PCI, Clapham PR, Crawford DH, Greaves MF, Weiss RA (1984) The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312:763–767
Doolittle RF, Feng DF, Johnson MS, McClure MA (1989) Origins and evolutionary relationships of retroviruses. Q Rev Biol 64:1–30
Feng DF, Johnson MS, Doolittle RF (1984) Aligning amino acid sequences: comparison of commonly used methods. J Mol Evol 21:112–125
Fetten JV, Roy N, Gilboa E (1991) A frameshift mutation at the NH2 terminus of the nucleoprotein gene does not affect generation of cytotoxic T lymphocyte epitopes. J Immunol 147:2697–2705
Fitzpatrick DR, Snider M, McDougall L, Beskorwayne T, Babiuk LA, Zamb TJ, Bielefeldt-Ohmann HB (1990) Molecular mimicry: a herpes virus glycoprotein antigenically related to a cell-surface glycoprotein expressed by macrophages, polymorphonuclear leukocytes, and platelets. Immunology 70:504–512
Gojobori T, Mariyama EN, Ina Y, Ikeo K, Miura T, Tsujimoto H, Hayami M, Yokoyama S (1990) Evolutionary origin of human and simian immunodeficiency viruses. Proc Natl Acad Sci USA 87:4108–4111
Golding H, Shearer GM, Hillman K, Lucas P, Manischewitz J, Zajac RA, Clerici M, Gress RE, Boswell RN, Golding B (1989) Common epitope in human immunodeficiency virus (HIV)1-gp41 and HLA class II elicits immunosuppressive autoantibodies capable of contributing to immune dysfunction in HIV 1-infected individuals. J Clin Invest 83:1430–1435
Gooding LR, Sofola IO, Tollefson AE, Duerksen-Hughes P, Wold WS (1990) The adenovirus E3-14.7K protein is a general inhibitor of tumor necrosis factor-mediated cytolysis. J Immunol 145:3080–3086
Gotoh O (1982) An improved algorithm for matching biological sequences. J Mol Biol 162:705–708
Guldner HH, Netter HJ, Szostecki C, Yaeger E, Will H (1990) Human anti-p68 autoantibodies recognize a common epitope of U1 RNA containing small nuclear ribonucleoprotein and influenza B virus. J Exp Med 171:819–829
Helene C (1987) Chimie et modulation selective de l'expression des genes. La vie des Sciences Comptes rendus 4:17–37
Jacks T, Madhani HD, Masiarz FR, Varmus HE (1988) Signals for ribosomal frameshifting in the Rous Sarcoma Virus gagpol region. Cell 55:447–458
Katz RA, Skalka AM (1990) Generation of diversity in retroviruses. Ann Rev Genet 24:409–445
Kieber-Emmons T, Jameson BA, Morrow WJ (1989) The gp120-CD4 interface: structural, immunological and pathological considerations. Biochim Biophys Acta 989:281–300
Klatzmann D, Champagne E, Chamaret S, Gruest J, Guetard D, Hercend T, Gluckman JC, Montagnier L (1984) T-lymphocyte T4 molecule behaves as the receptor for the human retrovirus. Nature 312:767–768
Kronenberg M (1991) Self-tolerance and autoimmunity. Cell 65:537–542
Lipman DJ, Pearson WR (1985) Rapid and sensitive protein similarity searchers. Science 227:1435–1441
Maddon PJ, Dalgleish AG, Mc Dougal JS, Clapham PR, Weiss RA, Axel R (1986) The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and in the brain. Cell 47:333–348
Moore KW, Vieira P, Fiorentino DF, Trounstine ML, Khan TA, Mosmann TR (1990) Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRF1. Science 248:1230–1234
Myers EW, Miller W (1988) Optimal alignments in linear space. CABIOS 4:11–17
Navia MA, Fitzgerald PMD, McKeever BM, Leu CT, Heimbach JC, Herber WK, Sigal IS, Darke PL, Springer JP (1989) Three-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-1. Nature 337:615–620
Needleman SB, Wunsch CD (1970) A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol 48:443–453
Oettinger MA, Schetz DG, Gorka C, Baltimore D (1990) RAG-1 and RAG-2 adjacent genes that synergistically activate V(D)J recombination. Science 248:1517–1523
Oldstone MB (1987) Molecular mimicry and autoimmune disease. Cell 50:819–820
Paque RE, Miller R (1991) Autoanti-idiotypes exhibit mimicry of myocyte antigens in virus-induced myocarditis. J Virol 65:16–22
Polard P, Prere MF, Chander M, Fayet O (1991) Programmed translational frameshifting and initiation at an AUU codon in gene expression of bacterial insertion sequence IS911. J Mol Biol 222:465–477
Prabhakar BS, Srinivasappa J, Beisel KW, Notkins AL (1988) Virus-induced autoimmunity: cross reactivity of antiviral antibodies with self components. In: Schultheiss HP (ed) New concepts in viral heart disease. Springer-Verlag, Heidelberg, pp 168–178
Schattner A, Rager-Zisman B (1990) Virus-induced autoimmunity. Rev Infect Dis 12:204–222
Yokoyama S (1988) Molecular evolution of the human and simian immunodeficiency viruses. Mol Biol Evol 5:645–659
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Facchiano, A., Facchiano, F. & van Renswoude, J. Divergent evolution may link human immunodeficiency virus GP41 to human CD4. J Mol Evol 36, 448–457 (1993). https://doi.org/10.1007/BF02406721
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DOI: https://doi.org/10.1007/BF02406721