Probing HIV dependence on host proteins
1 February 2008. Related: Basic science and immunology.
Richard Jefferys, TAG
An important new study has just been published in Science Express, the advance online section of the widely read journal Science. Abraham Brass and colleagues report results obtained using a genome-wide screen for host proteins necessary for HIV replication. The researchers used an approach that involves blocking the activity of known human genes using small slices of RNA called small interfering RNAs (siRNAs). A staggering 21,121 pools of four siRNAs per gene were employed in the study, ultimately revealing 273 host proteins that appear necessary for efficient HIV replication (the researchers have dubbed them HIV dependency factors or HDFs). [1]
Thirty-six HDFs comprise previously reported factors such as the CD4 and CXCR4 proteins, but the others are novel, including proteins involved in transporting materials into a cells nucleus, glycosylation (addition of sugar molecules to proteins, [2]) and degradation of cellular proteins [3].
One identified protein, ZNRD1, was also implicated in a recent study of genomic associations with viral load set point in people with HIV (mutations in the gene for ZNRD1 were associated with slow progression). [4]
So much data was generated that much of it is not in the paper but in the supplemental online material that accompanies it. [5] The authors also offer a busy schematic that gives a sense of the complex theater of virus-host interactions that they have raised the curtain on.
In an accompanying news story by Jon Cohen, a number of leading HIV researchers praise the paper and note that it offers a dazzling array of potential new leads for scientists looking to better understand the HIV life cycle, and how to inhibit it. [6]
Source: TAG Basic Science Blog (10 Jan 2008)
References:
- Brass A et al. Identification of Host Proteins Required for HIV Infection Through a Functional Genomic Screen. DOI: 10.1126/science.1152725. Published Online January 10, 2008 .
http://www.sciencemag.org/cgi/content/abstract/1152725 - http://en.wikipedia.org/wiki/Glycosylation
- http://en.wikipedia.org/wiki/Autophagy
- http://www.sciencemag.org/cgi/content/full/317/5840/944
- http://www.sciencemag.org/cgi/content/full/sci;1152725/DC1
- 6. http://www.sciencemag.org/cgi/content/full/319/5860/143