[A10001] Human immunodeficiency virus type 1 infection of neural cells involves a chemokine receptor dependent but CD4 independent entry

14th International AIDS Conference

Barcelona, Spain — July 7-12, 2002

[TITLE:] Human immunodeficiency virus type 1 infection of neural cells involves a chemokine receptor dependent but CD4 independent entry

[AUTHOR(S):] M.A. Muñoz-Fernández, S. Alvarez, C. Cantó-Nogués¹

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. A10001

BACKGROUND: HIV-1 infects the central nervous system and plays a direct role in the pathogenesis of AIDS dementia. However the mechanism by which HIV-1 can infect neurons continues being a controversy issue and thus it remains poorly understood.

METHODS: To address the mechanism by which HIV-1 infects neurons we have used human neuroblastoma (NB) cell lines. To identify the putative receptor, we also tested the cell surface expression of previously described receptors as CD4, nucleolin, galactosylceramide (GalC) and chemokine receptors, CCR1, CCR5 and CXCR4 by cell surface cytometry and by RT-PCR. We tested, by ELISA, the ability of the chemokines (MIP-1a, MIP-1b, RANTES, and SDF-1a), or antibodies to them to inhibit HIV-1 infection of NB lines.

RESULTS: Human neuronal cell lines (SK-N-SH and SK-N-MC) were found to be susceptible to productive infection by X4 or R5 HIV-1 isolates, as detected by viral load and p24 viral antigen. Cells express no CD4 and low levels of GalC or nucleolin. Furthermore, antibodies to any of these molecules did not affect NB infection. NB cells express variable levels of CCR5, CCR1 and CXCR4. Interestingly, exogenous heparan sulfate (HS) alone was able to substantially inhibit infection which an effect which was potentiated by RANTES or SDF-1 in the infection with R5 or X4 isolates. Besides, anti-CCR5 and anti-CXCR4 blocked significantly HIV-1 infection of R5 and X4 isolates respectively.

CONCLUSIONS: These results support an independent CD4 viral infection in neural cells and a role of HS in facilitating the interaction of chemokines with the cell surface and the consequent inhibition of HIV-1 infection. Our findings suggest a model in which initial interaction between a virion component, probably cyclophylin A, and/or gp120 to HS, is followed by binding to CCR5 or CXCR4 to internalize the virus. This would explain why the infection is so greatly inhibited by HS being chemokines able to potentiate this effect.

Presenting author: Ma Angeles Muñoz-Fernández

1Hospital General Univ Gregorio Marañón, Madrid, Spain.

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