Okada H, Wu X, Okada N, Irie RF; International Conference on AIDS.
Int Conf AIDS. 1998; 12: 517 (abstract no. 31112).
Nagoya City Univ. School of Medicine, Japan.
BACKGROUND: Some normal human sera contain natural IgM antibodies against Gg4 and GM2 which are capable of initiating complement-mediated cytolysis of HIV-1 virions and HIV-1-infected cells. In the present study we assessed anti-HIV activity of human IgM anti-GM2 monoclonal antibody (L55) to induce complement-mediated cytolysis to HIV-1 infected cells and virolysis. METHODS: HIV-1 infected human T cell line (MOLT4), monocyte cell line (U937) and human PBMC were analysed for expression of GM2 using L55 by fluorescence staining. L55 was then evaluated for its ability to cause lysis of HIV-1 infected human cell lines using 51Cr release assay and virions by p24 detection, and furthermore, to inhibit HIV-1 expansion in co-culture of HIV-infected U937 cells with naive cells and in co-culture of HIV patients' PMBC with seronegative PBMC in the presence of fresh human sera (FHS) as a complement source. HIV-1 infection was determined by detection of p24 in cells or in culture supernatants. RESULTS: HIV-1 infected MOLT4, U937 and human PBMC were shown to cause an increased expression of GM2 on their cell surface in a flow cytometry analysis. These infected cell lines were lysed strongly by L55 antibody in the presence of FHS. FHS alone did not show any cytolysis. L55 antibody also had the ability to lyse HIV virions via the complement activation. When L55 antibody and FHS were added to co-culture of HIV-infected U937 cells and naive cells, or to co-culture of HIV patients PMBC and seronegative PBMC, expansion of HIV-1 infection was delayed significantly. In a combined treatment experiment with azidothymidine (AZT) and L55 antibody plus FHS, their ability to suppress virus spread was synergized. CONCLUSION: Different from the agents such as RT inhibitors and proteinase inhibitors which cannot eliminate infected cells which already have incorporated HIV-1-genome, L55-induced complement mediated cytolysis could directly kill HIV-1-infected cells as well as HIV-1 virions. Therefore, treatment of HIV-1-infected patients with L55 could be effective to synergize with the effect of RT inhibitors or proteinase inhibitors in suppression of HIV in vivo.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Animals
- Anti-HIV Agents
- Antibodies, Monoclonal
- Complement System Proteins
- G(M2) Ganglioside
- HIV Infections
- HIV Seropositivity
- HIV-1
- Humans
- Paraproteins
- Virion
- Zidovudine
Other ID:
UI: 102229503
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