Volume 10 Supplement 1

Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts

Open Access

The interaction of HIV-1 and HIV-2 with cellular protein trafficking pathways

  • Justine Alford1,
  • Robert Spooner1,
  • Michela Marongiu1 and
  • Emma Anderson1
Retrovirology201310(Suppl 1):P2

https://doi.org/10.1186/1742-4690-10-S1-P2

Published: 19 September 2013

Background

Assembly and release of HIV-1 particles occurs at the plasma membrane and is dependent on trafficking of Gag from sites of protein synthesis to sites of particle assembly. For example, the interaction of HIV-1 Gag with components of cellular trafficking pathways such as clathrin adaptor proteins (AP) 1 and 3 has been shown to be required for HIV-1 virion production [1, 2]. This is likely to place a large burden on cellular trafficking pathways, but this has not previously been investigated. We addressed the questions of whether HIV-1 disrupts cellular protein trafficking and whether HIV-2 has the same effect.

Materials and methods

We used the well characterised pathways of diphtheria toxin (DTx) and ricin toxin (RTx) trafficking to measure the effect of HIV-1 and HIV-2 on toxin-induced inhibition of protein synthesis. HIV-1 and -2 Gag localisation, and the role of AP-3 in Gag trafficking, was studied using confocal immunofluorescence microscopy, siRNA-mediated knockdown of AP-3, and virion release assays.

Results

HIV-1 had a protective effect against DTx-, but not RTx-induced cytotoxicity, demonstrating that endosomal trafficking is specifically disrupted in the presence of HIV-1. However, HIV-2 had a significantly higher protective effect against DTx, suggesting greater disruption of endosomal trafficking by HIV-2. In agreement with these results, we observed a much higher proportion of HIV-2 Gag localised to endosomal compartments than HIV-1 Gag. There was strong co-localisation between HIV-2 Gag, AP-3 and clathrin, but less so with HIV-1 Gag. siRNA-mediated knockdown of AP-3 resulted in an increase in the proportion of both HIV-1 and HIV-2 Gag localised to endosomal compartments, a decrease in the proportion at the plasma membrane, and a reduction in virion release.

Conclusions

HIV-1 and HIV-2 both utilise cellular protein trafficking pathways, which disrupts normal cell functioning. HIV-2 has a particularly disruptive effect on the endosomal pathway, and we observed that HIV-2 Gag accumulates in endosomal compartments. AP-3 and clathrin are recruited to these compartments in the presence of HIV-2, and we hypothesise that this is a requirement for transport of Gag and/or virions from endosomes to the plasma membrane.

Declarations

Acknowledgements

This work was funded by the MRC.

Authors’ Affiliations

(1)
School of Life Sciences, University of Warwick

References

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Copyright

© Alford et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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