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. 1993 Dec;67(12):7711–7715. doi: 10.1128/jvi.67.12.7711-7715.1993

Molecular mimicry between the human immunodeficiency virus type 1 gp120 V3 loop and human brain proteins.

J R Trujillo 1, M F McLane 1, T H Lee 1, M Essex 1
PMCID: PMC238247  PMID: 8230494

Abstract

Immunologically cross-reactive proteins in the human brain that resemble the V3 loop of human immunodeficiency virus type 1 (HIV-1) gp120 have been identified. When several homogenized tissues from normal brains were used, a monoclonal antibody raised against amino acids 308 to 320 of the V3 loop reacted with three prominent human brain proteins (HBP) of 35, 55, and 110 kDa. Among the three, the 55-kDa HBP appears to be specific to the central nervous system. These results indicate that the V3 loop of HIV-1 gp120 shares an epitope with HBP. An immune response to the V3 loop that generates cross-reactive antibodies to cellular proteins may be an autoimmune mechanism by which HIV-1 can damage the central nervous system.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barin F., M'Boup S., Denis F., Kanki P., Allan J. S., Lee T. H., Essex M. Serological evidence for virus related to simian T-lymphotropic retrovirus III in residents of west Africa. Lancet. 1985 Dec 21;2(8469-70):1387–1389. doi: 10.1016/s0140-6736(85)92556-5. [DOI] [PubMed] [Google Scholar]
  2. Bourgoignie J. J., Pardo V. HIV-associated nephropathies. N Engl J Med. 1992 Sep 3;327(10):729–730. doi: 10.1056/NEJM199209033271012. [DOI] [PubMed] [Google Scholar]
  3. Clements G. J., Price-Jones M. J., Stephens P. E., Sutton C., Schulz T. F., Clapham P. R., McKeating J. A., McClure M. O., Thomson S., Marsh M. The V3 loops of the HIV-1 and HIV-2 surface glycoproteins contain proteolytic cleavage sites: a possible function in viral fusion? AIDS Res Hum Retroviruses. 1991 Jan;7(1):3–16. doi: 10.1089/aid.1991.7.3. [DOI] [PubMed] [Google Scholar]
  4. Dales S., Fujinami R. S., Oldstone M. B. Infection with vaccinia favors the selection of hybridomas synthesizing autoantibodies against intermediate filaments, one of them cross-reacting with the virus hemagglutinin. J Immunol. 1983 Sep;131(3):1546–1553. [PubMed] [Google Scholar]
  5. Emini E. A., Schleif W. A., Nunberg J. H., Conley A. J., Eda Y., Tokiyoshi S., Putney S. D., Matsushita S., Cobb K. E., Jett C. M. Prevention of HIV-1 infection in chimpanzees by gp120 V3 domain-specific monoclonal antibody. Nature. 1992 Feb 20;355(6362):728–730. doi: 10.1038/355728a0. [DOI] [PubMed] [Google Scholar]
  6. Freed E. O., Myers D. J., Risser R. Identification of the principal neutralizing determinant of human immunodeficiency virus type 1 as a fusion domain. J Virol. 1991 Jan;65(1):190–194. doi: 10.1128/jvi.65.1.190-194.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fujinami R. S., Oldstone M. B. Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science. 1985 Nov 29;230(4729):1043–1045. doi: 10.1126/science.2414848. [DOI] [PubMed] [Google Scholar]
  8. Fujinami R. S., Oldstone M. B. Molecular mimicry as a mechanism for virus-induced autoimmunity. Immunol Res. 1989;8(1):3–15. doi: 10.1007/BF02918552. [DOI] [PubMed] [Google Scholar]
  9. Fujinami R. S., Oldstone M. B., Wroblewska Z., Frankel M. E., Koprowski H. Molecular mimicry in virus infection: crossreaction of measles virus phosphoprotein or of herpes simplex virus protein with human intermediate filaments. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2346–2350. doi: 10.1073/pnas.80.8.2346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Garry R. F., Koch G. Tat contains a sequence related to snake neurotoxins. AIDS. 1992 Dec;6(12):1541–1542. doi: 10.1097/00002030-199212000-00019. [DOI] [PubMed] [Google Scholar]
  11. Garry R. F., Kort J. J., Koch-Nolte F., Koch G. Similarities of viral proteins to toxins that interact with monovalent cation channels. AIDS. 1991 Nov;5(11):1381–1384. doi: 10.1097/00002030-199111000-00017. [DOI] [PubMed] [Google Scholar]
  12. Hoffmann G. W., Kion T. A., Grant M. D. An idiotypic network model of AIDS immunopathogenesis. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3060–3064. doi: 10.1073/pnas.88.8.3060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Horwitz M. S., Boyce-Jacino M. T., Faras A. J. Novel human endogenous sequences related to human immunodeficiency virus type 1. J Virol. 1992 Apr;66(4):2170–2179. doi: 10.1128/jvi.66.4.2170-2179.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hwang S. S., Boyle T. J., Lyerly H. K., Cullen B. R. Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1. Science. 1991 Jul 5;253(5015):71–74. doi: 10.1126/science.1905842. [DOI] [PubMed] [Google Scholar]
  15. Javaherian K., Langlois A. J., LaRosa G. J., Profy A. T., Bolognesi D. P., Herlihy W. C., Putney S. D., Matthews T. J. Broadly neutralizing antibodies elicited by the hypervariable neutralizing determinant of HIV-1. Science. 1990 Dec 14;250(4987):1590–1593. doi: 10.1126/science.1703322. [DOI] [PubMed] [Google Scholar]
  16. Javaherian K., Langlois A. J., McDanal C., Ross K. L., Eckler L. I., Jellis C. L., Profy A. T., Rusche J. R., Bolognesi D. P., Putney S. D. Principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6768–6772. doi: 10.1073/pnas.86.17.6768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kimmel P. L., Phillips T. M., Ferreira-Centeno A., Farkas-Szallasi T., Abraham A. A., Garrett C. T. Brief report: idiotypic IgA nephropathy in patients with human immunodeficiency virus infection. N Engl J Med. 1992 Sep 3;327(10):702–706. doi: 10.1056/NEJM199209033271006. [DOI] [PubMed] [Google Scholar]
  18. Kion T. A., Hoffmann G. W. Anti-HIV and anti-anti-MHC antibodies in alloimmune and autoimmune mice. Science. 1991 Sep 6;253(5024):1138–1140. doi: 10.1126/science.1909456. [DOI] [PubMed] [Google Scholar]
  19. Kumar M., Resnick L., Loewenstein D. A., Berger J., Eisdorfer C. Brain-reactive antibodies and the AIDS dementia complex. J Acquir Immune Defic Syndr. 1989;2(5):469–471. [PubMed] [Google Scholar]
  20. LaRosa G. J., Davide J. P., Weinhold K., Waterbury J. A., Profy A. T., Lewis J. A., Langlois A. J., Dreesman G. R., Boswell R. N., Shadduck P. Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant. Science. 1990 Aug 24;249(4971):932–935. doi: 10.1126/science.2392685. [DOI] [PubMed] [Google Scholar]
  21. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  22. Linsley P. S., Ledbetter J. A., Kinney-Thomas E., Hu S. L. Effects of anti-gp120 monoclonal antibodies on CD4 receptor binding by the env protein of human immunodeficiency virus type 1. J Virol. 1988 Oct;62(10):3695–3702. doi: 10.1128/jvi.62.10.3695-3702.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Matsiota P., Chamaret S., Montagnier L., Avrameas S. Detection of natural autoantibodies in the serum of anti-HIV-positive individuals. Ann Inst Pasteur Immunol. 1987 Mar-Apr;138(2):223–233. doi: 10.1016/s0769-2625(87)80073-9. [DOI] [PubMed] [Google Scholar]
  24. Matsuda Z., Chou M. J., Matsuda M., Huang J. H., Chen Y. M., Redfield R., Mayer K., Essex M., Lee T. H. Human immunodeficiency virus type 1 has an additional coding sequence in the central region of the genome. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6968–6972. doi: 10.1073/pnas.85.18.6968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Matsushita S., Robert-Guroff M., Rusche J., Koito A., Hattori T., Hoshino H., Javaherian K., Takatsuki K., Putney S. Characterization of a human immunodeficiency virus neutralizing monoclonal antibody and mapping of the neutralizing epitope. J Virol. 1988 Jun;62(6):2107–2114. doi: 10.1128/jvi.62.6.2107-2114.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Moore J. P., Ho D. D. Antibodies to discontinuous or conformationally sensitive epitopes on the gp120 glycoprotein of human immunodeficiency virus type 1 are highly prevalent in sera of infected humans. J Virol. 1993 Feb;67(2):863–875. doi: 10.1128/jvi.67.2.863-875.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. O'Brien W. A., Koyanagi Y., Namazie A., Zhao J. Q., Diagne A., Idler K., Zack J. A., Chen I. S. HIV-1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4-binding domain. Nature. 1990 Nov 1;348(6296):69–73. doi: 10.1038/348069a0. [DOI] [PubMed] [Google Scholar]
  28. Price R. W., Brew B., Sidtis J., Rosenblum M., Scheck A. C., Cleary P. The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science. 1988 Feb 5;239(4840):586–592. doi: 10.1126/science.3277272. [DOI] [PubMed] [Google Scholar]
  29. Sellal F., Hirsch E., Lisovoski F., Mutschler V., Collard M., Marescaux C. Contralateral disappearance of parkinsonian signs after subthalamic hematoma. Neurology. 1992 Jan;42(1):255–256. doi: 10.1212/wnl.42.1.255. [DOI] [PubMed] [Google Scholar]
  30. Sharpless N. E., O'Brien W. A., Verdin E., Kufta C. V., Chen I. S., Dubois-Dalcq M. Human immunodeficiency virus type 1 tropism for brain microglial cells is determined by a region of the env glycoprotein that also controls macrophage tropism. J Virol. 1992 Apr;66(4):2588–2593. doi: 10.1128/jvi.66.4.2588-2593.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shepley M. P., Sherry B., Weiner H. L. Monoclonal antibody identification of a 100-kDa membrane protein in HeLa cells and human spinal cord involved in poliovirus attachment. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7743–7747. doi: 10.1073/pnas.85.20.7743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Shioda T., Levy J. A., Cheng-Mayer C. Macrophage and T cell-line tropisms of HIV-1 are determined by specific regions of the envelope gp120 gene. Nature. 1991 Jan 10;349(6305):167–169. doi: 10.1038/349167a0. [DOI] [PubMed] [Google Scholar]
  33. Simmonds P., Balfe P., Ludlam C. A., Bishop J. O., Brown A. J. Analysis of sequence diversity in hypervariable regions of the external glycoprotein of human immunodeficiency virus type 1. J Virol. 1990 Dec;64(12):5840–5850. doi: 10.1128/jvi.64.12.5840-5850.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Skinner M. A., Langlois A. J., McDanal C. B., McDougal J. S., Bolognesi D. P., Matthews T. J. Neutralizing antibodies to an immunodominant envelope sequence do not prevent gp120 binding to CD4. J Virol. 1988 Nov;62(11):4195–4200. doi: 10.1128/jvi.62.11.4195-4200.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Srinivasappa J., Saegusa J., Prabhakar B. S., Gentry M. K., Buchmeier M. J., Wiktor T. J., Koprowski H., Oldstone M. B., Notkins A. L. Molecular mimicry: frequency of reactivity of monoclonal antiviral antibodies with normal tissues. J Virol. 1986 Jan;57(1):397–401. doi: 10.1128/jvi.57.1.397-401.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Takahashi H., Nakagawa Y., Pendleton C. D., Houghten R. A., Yokomuro K., Germain R. N., Berzofsky J. A. Induction of broadly cross-reactive cytotoxic T cells recognizing an HIV-1 envelope determinant. Science. 1992 Jan 17;255(5042):333–336. doi: 10.1126/science.1372448. [DOI] [PubMed] [Google Scholar]
  37. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Werner T., Ferroni S., Saermark T., Brack-Werner R., Banati R. B., Mager R., Steinaa L., Kreutzberg G. W., Erfle V. HIV-1 Nef protein exhibits structural and functional similarity to scorpion peptides interacting with K+ channels. AIDS. 1991 Nov;5(11):1301–1308. doi: 10.1097/00002030-199111000-00003. [DOI] [PubMed] [Google Scholar]
  39. Yamada M., Zurbriggen A., Oldstone M. B., Fujinami R. S. Common immunologic determinant between human immunodeficiency virus type 1 gp41 and astrocytes. J Virol. 1991 Mar;65(3):1370–1376. doi: 10.1128/jvi.65.3.1370-1376.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Yuan X., Matsuda Z., Matsuda M., Essex M., Lee T. H. Human immunodeficiency virus vpr gene encodes a virion-associated protein. AIDS Res Hum Retroviruses. 1990 Nov;6(11):1265–1271. doi: 10.1089/aid.1990.6.1265. [DOI] [PubMed] [Google Scholar]

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