Email updates

Keep up to date with the latest news and content from Virology Journal and BioMed Central.

Open Access Research

Loss of Niemann Pick type C proteins 1 and 2 greatly enhances HIV infectivity and is associated with accumulation of HIV Gag and cholesterol in late endosomes/lysosomes

Ebony M Coleman12, Tiffany N Walker1 and James EK Hildreth12*

Author Affiliations

1 Center for AIDS Health Disparities Research, Meharry Medical College, Nashville, TN, USA

2 Department of Molecular and Cellular Biology, University of California, Davis, CA, USA

For all author emails, please log on.

Virology Journal 2012, 9:31  doi:10.1186/1743-422X-9-31

Published: 24 January 2012

Abstract

Background

Cholesterol pathways play an important role at multiple stages during the HIV-1 infection cycle. Here, we investigated the role of cholesterol trafficking in HIV-1 replication utilizing Niemann-Pick Type C disease (NPCD) cells as a model system.

Results

We used a unique NPC2-deficient cell line (NPCD55) that exhibited Gag accumulation as well as decreased NPC1 expression after HIV infection. Virus release efficiency from NPCD55 cells was similar to that from control cells. However, we observed a 3 to 4-fold enhancement in the infectivity of virus released from these cells. Fluorescence microscopy revealed accumulation and co-localization of Gag proteins with cholesterol in late endosomal/lysosomal (LE/L) compartments of these cells. Virion-associated cholesterol was 4-fold higher in virions produced in NPCD55 cells relative to virus produced in control cells. Treatment of infected NPCD55 cells with the cholesterol efflux-inducing drug TO-9013171 reduced virus infectivity to control levels.

Conclusions

These results suggest cholesterol trafficking and localization can profoundly affect HIV-1 infectivity by modulating the cholesterol content of the virions.