113 ADIPOCYTES AND PRE-ADIPOCYTES ARE NOT PRODUCTIVELY INFECTED BY HIV-1 G Bélanger-Jasmin1, S Selliah1, A Chamberland1, F Giguel2, C Tremblay1 Several mechanisms have been postulated to explain the fat redistribution associated with lipodystrophy, including mitochondrial toxicity from nucleoside analogs and alterations of metabolic pathways by protease inhibitors. However, lipodystrophy has been observed in treatment-naive subjects, suggesting that HIV-1 itself may also be an important component of this syndrome. HIV-1 infectivity of adipocytes has not been convincingly demonstrated. This study's goal was to assess the infectivity of HIV-1 in human adipocytes and pre-adipocytes, to determine whether HIV-1 could exert a direct effect on these cells and to evaluate whether HIV-1 could affect the maturation of these cells. We attempted to infect human adipocytes and pre-adipocytes using R5 and X4 HIV-1 clinical isolates as well as the lab strain IIIB. We evaluated infectivity by measuring HIV-1 p24 antigen production, by observation for cytopathic effects and by PCR assessment of HIV-1 DNA. We also evaluated expression of cell receptors associated with HIV entry such as CD4, CXCR4 and CCR5 using immunohistochemistry. We analyzed expression of transcription factors by micro-array analysis.
1Hôpital St-Luc du CHUM, Montréal, Québec; 2Massachusetts General Hospital, Boston, USA
There was no conclusive evidence of productive infection of these cells. A transient minimal rise in HIV-1 p24 production was observed 24-48 hours post infection, which decreased over time. No cytopathic effects were observed on microscopic evaluation. Cell pellets harvested at the end of the culture were negative for HIV-1 DNA. Both pre-adipocytes and adipocytes were negative for CD4 expression. Pre-adipocytes did not express CCR5 or CXCR4 by IHS. However, mature adipocytes were positive for both CCR5 and CXCR4. Data on micro-array analysis will be presented.
We conclude that even if mature adipocytes express receptors permissive for HIV entry, under our experimental conditions, human pre-adipocytes and adipocytes are not productively infected by HIV-1. However, HIV-1 entry into these cells via an endosomal pathway need to be further assessed. We therefore cannot rule out an active role of HIV-1 in adipocyte metabolism.