Summary
During the last decade, research efforts have been aimed at development of an HIV vaccine. Until now it has not been possible to identify conserved epitopes on the envelope structure of HIV, which might be targets for neutralizing antibodies. However, it is clear that the conformation of gp120 is important for the development of broadly neutralizing antibodies, and that glycan structures of gp120 are of importance in this context. HIV-infected patients are often co-infected with other viruses, and one mechanism for expanding the cellular tropism of HIV in vitro is through formation of phenotypically mixed particles (pseudotypes) with HTLV-I. Previously, pseudotypes were found to allow penetration of HIV particles into CD4-negative cells, which are otherwise nonsusceptible to HIV infection. In the search for epitopes that might be the target for an HIV vaccine, the pseudotype phenomenon should be taken into account. An HIV-neutralizing antibody, induced by a vaccine, should also be able to neutralize potential pseudotypes. The in vitro infection of CD4-negative cells with pseudotypes could be blocked with anti-HTLV-I serum, but failed to be significantly inhibited with antibodies directed at HIV. These findings suggest that pseudotypes may represent a way to escape neutralization by the immune system in vivo. Previous reports have indicated that carbohydrate structures may be conserved neutralization epitopes on retroviruses. Lectins and monoclonal antibodies directed to carbohydrate structures were found to block HIV/HTLV-I pseudotype infection in CD4-negative cells. Therefore, although viral cofactors might expand the tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate neutralization epitopes. Taken together, these results indicate that carbohydrate structures might induce protective antibodies, in spite of HIV envelope protein variability and the possibility of pseudotype production, which is why the results may be used in the search of an HIV vaccine or immune-stimulating agents.
Similar content being viewed by others
References
Barré-Sinoussi, F., Chermann, J.C., Rey, F., Nugeyre, M.T., Chamaret, S., Gruest, J., Dauguet, C., Axler-Blin, C., Vézinet-Brun, F., Rouzioux, C., Rozenbaum, W. and Montagnier, L., Science, 220 (1983) 868.
Popovic, M., Sarnagadharan, M.G., Read, E. and Gallo, R.C., Science, 224 (1984) 497.
Klatzmann, D., Barré-Sinoussi, F., Nugeyre, M.T., Dauguet, C., Vilmer, E., Griscelli, C., Brun-Vézinet, F., Rouzioux, C., Gluckman, J.C., Chermann, J.C. and Montagnier, L., Science, 225 (1984) 59.
Fenouillet, E., Clerget-Raslain, B., Gluckman, J.C., Guétard, D., Montagnier, L. and Bahraou, E., J. Exp. Med., 169 (1989) 807.
DeVita, V.T. (Ed.) AIDS Etiology, Diagnosis, Treatment, and Prevention, 3rd ed., J.B. Lippincott Company, Philadelphia, PA, 1992.
Cheng-Mayer, C., Rutka, J.T., Rosenblum, M.L., McHugh, T., Stites, D.P. and Levy, J.A., Proc. Natl. Acad. Sci. USA, 84 (1987) 3526.
Harouse, J.M., Bhat, S., Spitalnik, D.H., Laughlin, M., Stefano, K., Silberberg, D.H. and Gonzalez-Scarano, F., Science, 253 (1991) 320.
Harouse, J.M., Kunsch, C., Hartle, H.T., Laughlin, M.A., Hoxie, J.A., Wigdahl, B. and Gonzalez-Scarano, F., J. Virol., 63 (1989) 2527.
Harouse, J.M., Laughlin, M., Pletcher, C., Friedman, H.M. and Gonzalez-Scarano, F.J., Leuco. Biol., 49 (1991) 605.
Li, X.L., Moudgil, T., Vinters, H.V. and Ho, D.D., J. Virol., 64 (1990) 1383.
Ho, D.D., Neumann, A.U., Perelson, A.S., Chen, W., Leonard, J.M. and Markowitz, M., Nature, 373 (1995) 123.
Wei, X., Ghosh, S.K., Taylor, M.E., Johnson, V.A., Emini, E.A., Deutsch, P., Lifson, J.D., Bonhoeffer, S., Nowak, M.A., Hahn, B.H., Saag, M.S. and Shaw, G.M., Nature, 373 (1995) 117.
Goudsmit, J., Back, N.K.T. and Nara, P.L., FASEB J., 5 (1991) 2427.
Moore, J.P., Cao, Y., Qing, L., Sattentau, Q.J., Pyati, J., Koduri, R., Robinson, J., Barbas, C.F., Burton, D.R. and Ho, D.D., J. Virol., 69 (1995) 101.
Cohen, J., Science, 264 (1994) 1072.
Poiesz, B.J., Ruscetti, F.V., Gazdar, A.F., Bunn, A.F., Minna, J.D. and Gallo, R.C., Proc. Natl. Acad. Sci. USA, 77 (1980) 7415.
Moore, J.P., Sattentau, Q.J., Wyatt, R. and Sodroski, J., J. Virol., 68 (1994) 469.
Cavacini, L., Emes, C.L., Power, J., Underdahl, J., Goldstein, R., Mayer, K. and Posner, M.R., J. Acquired Immune Defic. Syndr., 6 (1993) 1093.
Goudsmit, J., Debouck, C., Meloen, R.H., Smit, L., Bakker, M., Asher, D.M., Wolff, A.V., Gibbs Jr., C.J. and Carleton, G.D., Proc. Natl. Acad. Sci. USA, 85 (1988) 4478.
McKeating, J.A., Goudsmit, J., Pearl, L.H., Mulder, C. and Weiss, R.A., Aids, 3 (1988) 777.
Weiss, R.A., Clapham, P.R., McClure, M.O., McKeating, J.A., McKnight, A., Dalgleish, A.G., Sattentau, Q.J. and Weber, J.N., J. Acquired Immune Defic. Syndr., 1 (1988) 536.
Hansen, J.E.S., Clausen, H., Nielsen, C., Teglbjærg, L.S., Hansen, L.L., Nielsen, C.M., Dabelsteen, E., Mathiesen, L.R., Hakomori, S.I. and Nielsen, J.O., J. Virol., 64 (1990) 2833.
Hansen, J.E.S., Apmis, 100 (1992) 96.
Pique, C., Pham, D., Tursz, T. and Dokhélar, M.C., J. Virol., 66 (1992) 906.
Lusso, P., Lori, F. and Gallo, R.C., J. Virol., 64 (1990) 6341.
Spector, D.H., Wade, E., Wright, D.A., Koval, V., Clark, C., Jaquish, D. and Spector, S.A., J. Virol., 64 (1990) 2298.
Cann, A.J., Churcher, M.J., Boyd, M., O'Brien, W., Zhao, J.Q., Zack, J. and Chen, I.S.Y., J. Virol., 66 (1992) 305.
Bartolomew, C., Blattner, W. and Cleghorn, F., Lancet, (1987) 1469.
Bartolomew, C., Saxinger, C., Clark, J.W., Gail, M., Dudgeon, A., Mahabir, B., Hull-Drysdale, B., Cleghorn, F., Gallo, R.C. and Blattner, W.A., J. Am. Med. Assoc., 257 (1987) 2604.
Hattori, S., Kiyokawa, T., Imagawa, K., Shimizu, F., Hashimura, E., Seiki, M. and Yoshida, M., Virology, 136 (1984) 338.
Lee, T.H., Coligan, J.E., Homma, T., McLane, M.F., Tachibana, N. and Essex, M., Proc. Natl. Acad. Sci. USA, 81 (1984) 3856.
Cann, A.J. and Chen, I.S.Y., in Field, B.N. (Ed.), Virology, 2nd ed., Vol. 2, Raven Press, New York, NY, 1990, p. 1501.
Takehara, N., Iwahara, Y., Uemura, Y., Sawada, T., Ohtsuki, Y., Iwai, H., Hoshino, H. and Miyoshi, I., Int. J. Cancer, 44 (1989) 332.
Gray, G.S., White, M., Bartman, T. and Mann, D., Virology, 177 (1990) 391.
Paine, E., Garcia, J., Philpott, T.C., Shaw, G. and Ratner, L., Virology, 182 (1991) 111.
Starcich, B.R., Hahn, B.H., Shaw, G.M., McNeely, P.D., Modrow, S., Wolf, H., Parks, E.S., Parks, W.P., Josephs, S.F., Gallo, R.C. and Wong-Staal, F., Cell, 45 (1986) 637.
Schulz, T.F., Calabrò, M.L., Hoad, J.G., Carrington, C.V.F., Matutes, E., Catovsky, D. and Weiss, R.A., Virology, 184 (1991) 483.
Watkins, B.A., Reitz, M.S., Wilson, C.A., Aldrich, K., Davis, A.E. and Robert-Guroff, M., J. Virol., 67 (1993) 7493.
Leonard, C.K., Spellman, W.M., Riddle, L., Harris, R.J., Thomas, N.J. and Gregory, J.T., J. Biol. Chem., 265 (1990) 10737.
Hansen, J.E.S., Nielsen, C., Arendrup, M., Olofsson, S., Mathiesen, L.R., Nielsen, J.O. and Clausen, H., J. Virol., 65 (1991) 6461.
Morikawa, Y., Overton, H., Moore, J.P., Wilkinson, A.J., Brady, R.L., Lewis, S.J. and Jones, I.M., Aids Res. Hum. Retroviruses, 6 (1990) 765.
Gruters, R.A., Neefjes, J.J., Tersmette, M., De Goede, R.E.Y., Tulp, A., Huisman, H.G., Miedema, F. and Ploegh, H.L., Nature, 330 (1987) 74.
Fenouillet, E. and Gluckman, J.C., J. Gen. Virol., 72 (1991) 1919.
Sørensen, A.M.M., Nielsen, C., Arendrup, M., Clausen, H., Nielsen, J.O., Osinaga, E., Roseto, A. and Hansen, J.E.S., J. Acquired Immune Defic. Syndr., 7 (1994) 116.
Back, N.K.T., Smit, L., De Jong, J.J., Keulen, W., Schutten, M., Goudsmit, J. and Tersmette, M., Virology, 199 (1994) 431.
Nara, P.L., Garrity, R.R. and Goudsmit, J., FASEB J., 5 (1991) 2437.
Fenouillet, E., Gluckman, J.C. and Jones, I.M., Trends Biochem. Sci., 19 (1994) 65.
Fultz, P.N., Nara, P., Barré-Sinouissi, F., Chaput, A., Greenberg, M., Muchmore, E., Kieny, M.P. and Girard, M., Science, 256 (1992) 1687.
Cao, Y., Qin, L., Zhang, L., Safrit, J. and Ho, D.D., New Engl. J. Med., 332 (1995) 201.
Hilleman, M.R., Aids Res. Hum. Retroviruses, 10 (1994) 1409.
Haynes, B.F., Science, 260 (1993) 1279.
Macilwain, C., Nature, 369 (1994) 593.
Graham, B.S. and Wright, P.F., New Engl. J. Med., 333 (1995) 1331.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sørensen, A.M.M. Neutralization epitopes on HIV pseudotyped with HTLV-I. Perspectives in Drug Discovery and Design 5, 154–160 (1996). https://doi.org/10.1007/BF02174010
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02174010