AEGiS-07IAC: Potential role for complement receptor 2 (CR2) in complement (C) mediated enhancement of HIV in vitro and in vivo.

7th International AIDS Conference

Florence, Italy — June 16-21, 1991

Potential role for complement receptor 2 (CR2) in complement (C) mediated enhancement of HIV in vitro and in vivo.

Int Conf AIDS 1991 Jun 16-21; 7:97 (abstract no. M.A.1021)
June R, Spear G, Stefanik K, Lint T, Landay AL; Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois, USA

OBJECTIVE: This study was designed to determine the mechanism of complement mediated enhancement of HIV-1 infection by monitoring provirus formation and virus binding. It also characterized a population of T lymphocytes in vivo which expressed the receptors required for enhancement.

METHODS: Supernatants containing HIV/RF were incubated with anti-HIV antibody (Ab) and/or C for 1 hr. at 37 degrees C. Cells (MT2 or Peripheral blood lymphocytes (PBL)) were then added and incubated an additional 4 hr. The cells were washed, cultured for 3-7 days and evaluated for HIV-antigen (Ag), reverse transcriptase (RT) activity, or provirus formation by polymerase chain reaction. To assess virion binding, Ab and C treated virus was incubated with cells on ice for 1 hr. followed by immediate cell lysis to evaluate bound HIV-Ag. Complement receptors on PBL were characterized by two and three color flow cytometry.

RESULTS: HIV-Ag production and RT activity of MT2 cells and PBL enriched for CD4+ lymphocytes infected with virus pre-treated with Ab and C was significantly greater than that of cells infected with virus alone, or virus treated with Ab or C separately. This increased HIV-Ag and RT production correlated with provirus formation and HIV binding. Flow cytometric studies of PBL from healthy volunteers demonstrated co-expression of CD4 and CR2. Three color flow cytometric evaluation of this population demonstrated co-expression of CD45RA, CD45RO dim, and CD29 intermediate. The co-expression of CR2 on CD4+ lymphocytes was decreased by 60% in HIV infected individuals.

CONCLUSIONS: We have directly shown that the increased HIV-Ag production seen in cells infected by Ab plus C treated HIV is due to increased binding of virus to cell surfaces and increased infection. We have also shown that a population of lymphocytes exists in vivo which may be capable of exhibiting complement mediated enhancement. These cells were found to be decreased in AIDS patients.

Keywords: AEGIS, Receptors, Complement 3d, Complement, HIV Antibodies, Antigens, CD4, Receptors, Complement, HIV Infections, Acquired Immunodeficiency Syndrome, HIV Antigens, Antigens, CD45, CD4-Positive T-Lymphocytes, RNA-Directed DNA Polymerase, Proviruses, T-Lymphocytes, Antibodies, Antigens, CD29, In Vitro, Human, ICA7
910616
MA1021