Two parallel routes of the complement-mediated antibody-dependent enhancement of HIV-1 infection

Zoltán Prohászka, József Nemes, Tünde Hidvégi, Ferenc D. Tóth, Krisztina Kerekes, Anna Erdei, Judit Szabó, Eszter Ujhelyi, Nicole Thielens, Manfred P. Dierich, Peter Späth, Berhane Ghebrehiwet, Hartmut Hampl, Jolán Kiss, Gerard Arlaud, George Füst

Research output: Article

29 Citations (Scopus)

Abstract

Objective: To study the mechanism of the complement-mediated antibody-dependent enhancement (C'-AD) of HIV infection which may play a significant role in the progression of HIV-disease. Methods: In vitro complement activating and complement-mediated HIV-infection enhancing abilities of three human anti-gp41 monoclonal antibodies (MAb) were tested. C'-ADE was estimated using HIV-1(IIIB) and CR2 (CD21)-carrying MT-4 target cells. Normal human serum (NHS), purified C1q, C1q-deficient (C1qD) and C2-deficient (C2D) human sera were applied as complement sources. Results: All MAb mediated increased C1q binding to solid-phase gp41. All MAb had a marked dose-dependent and strictly complement-mediated HIV-infection enhancing effect. Mixtures of the MAb with purified C1q also significantly increased HIV-1 infection. C1qD serum had a markedly lower enhancing effect than NHS, which could be raised to normal level by addition of purified C1q. Pretreatment of the target cells with anti-CR2 antibodies only partially inhibited the enhancing effect of the MAb plus normal human serum. Conclusion: These novel findings indicate that besides the well-known facilitation of entry of HIV-1 by the interaction between virus-bound C3 fragments and CR2 present on the target cells, fixation of C1q to intact virions also results in an enhanced productive HIV-1 infection in the MT-4 cell cultures.

Original languageEnglish
Pages (from-to)949-958
Number of pages10
JournalAIDS
Volume11
Issue number8
DOIs
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Prohászka, Z., Nemes, J., Hidvégi, T., Tóth, F. D., Kerekes, K., Erdei, A., Szabó, J., Ujhelyi, E., Thielens, N., Dierich, M. P., Späth, P., Ghebrehiwet, B., Hampl, H., Kiss, J., Arlaud, G., & Füst, G. (1997). Two parallel routes of the complement-mediated antibody-dependent enhancement of HIV-1 infection. AIDS, 11(8), 949-958. https://doi.org/10.1097/00002030-199708000-00002