AEGiS-12IAC: Study of the phenotype of primary HIV-1 isolates and their susceptibility to neutralization by polyclonal sera.

12th International AIDS Conference

Geneva, Switzerland - June 28-July 3, 1998

Study of the phenotype of primary HIV-1 isolates and their susceptibility to neutralization by polyclonal sera.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:24 (abstract no. 11211)

Nyambi P, Beirnaert E, Dayaraj C, Kengasong J, Zolla-Pazner S, Van der Groen G
VA Medical Center, New York, NY 1001-5050, USA.

OBJECTIVE: To study the correlation between syncytium induction in MT2 cells and coreceptor usage of primary HIV-1 isolates, and to determine their susceptibility to neutralization by homologous and heterologous polyclonal sera.

MATERIALS AND METHODS: Sixteen HIV-1 isolates, 13 from group M (subtypes A-H) and three from group O, with 12 homologous and 2 heterologous sera were studied. The syncytium inducing properties of the viruses were investigated in MT2 cell lines. Coreceptor usage (CCR5 and CXCR4) was determined on GHOST cells (HOS cells with CD4, CCR5 or CXCR4 and GFP as the indicator gene). Neutralization was performed with 3 day PHA-stimulated PBMCs. Serum as well as isolate neutralization clusters were defined by spectral map analysis (Nyambi et al, J Virol 1996; 70: 6235-43).

RESULTS: The syncytium inducing abilities of the viruses correlated well with coreceptor usage. Ten of 16 NSI isolates were CCR5-tropic (R5 type). Of the six SI isolates, four were dual-tropic (using both CXCR4 and CCR5, X4R5 type), and two were CXCR4-tropic (R4 type). The isolate neutralization clusters contained either primary HIV-1 isolates of the R5 (cluster I and IV), R5 and X4R5 (cluster II), X4 and X4R5 (cluster III) type of viruses. The total of the average neutralizing capacity of sera from individuals infected with X4 and X4R5 was -1.8 for R5 and +2.0 for X4 and X4R5 type of viruses, regardless the HIV-1 subtype they belong to.

CONCLUSION: The syncytium inducing properties (NSI, SI on MT2 cells) correlated well with coreceptor usage on GHOST cells. NSI isolates were exclusively R5, while SI isolates were either X4 or X4R5. Generalist potent sera neutralized HIV-1 isolates irrespective of their coreceptor usage. Specialist potent sera of individuals infected with X4 and X4R5 type of primary HIV-1 isolates neutralized specialist X4 and X4R5 type better than R5 type of viruses, and vice versa.

Keywords: AEGIS, HIV-1, Phenotype, Giant Cells, Disease Susceptibility, Cell Line, genetics, ICA12
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