Image: C. Goldsmith, P. Feorino, E. L. Palmer, W. R. McManus, CDC/flickr
Image: C. Goldsmith, P. Feorino, E. L. Palmer, W. R. McManus, CDC/flickr

Stress granules are clusters of RNA and proteins that cells assemble as a protective measure against environmental stresses and viral infections. Research led by Dr. Andrew Mouland, of the Lady Davis Institute at the Jewish General Hospital and the McGill University AIDS Centre, reveals that HIV-1 is capable of resisting these stress granules by blocking the cell’s ability to assemble them in its effort to fight off the virus. Moreover, it is able to disassemble pre-existing stress granules, which enhances its replicative capacity and further weakens the cell. The finding is published in the respected Nature Communications, and constitutes an unexpected facet of how HIV-1 commandeers the host cell’s antiviral stress response.

“It is a huge advantage for the virus to be able to prevent the cell from, in effect, summoning reinforcements to help it fight off HIV-1 infection,” explains Dr. Mouland, Associate Professor of Medicine at McGill University. “Using biochemical and genetic analysis, along with advanced microscopy, we uncovered the mechanism by which HIV-1 blocks stress granule assembly,”
His lab examined cells obtained from actual HIV-1-infected patients in order to ascertain that the virus was employing this technique in its arsenal to survive and thrive. The fact that this process has been observed in vivo is as strong an indicator as possible that it is important to the biology of the virus.
“We believe that HIV-1 actively elicits these changes to the cell in order to enhance replication,” said Dr. Mouland. “Our work proposes to answer the question of how stress granules assemble and how they can be disassembled, two highly significant and elusive questions hanging over our field. Because they are an essential response to so many different stresses on the cell, the knowledge we’re gathering will have relevance for other viral diseases, as well as for neurological conditions including Alzheimer’s, dementia, and amyotrophic lateral sclerosis (Lou Gehrig’s disease).”
As the authors wrote in their paper, “Understanding how HIV-1 counters anti-viral stress responses will lay the groundwork for new therapeutic strategies to bolster host cell immune defences against HIV-1 and other pathogens.”
“eEF2 and Ras-GAP SH3 domain-binding protein (G3BP1) modulate stress granule assembly during HIV-1 infection,” by Fernando Valiente-Echeverria, et al is published in Nature Communications 5:4819 doi: 10.1038/ncomms5819 (2014).

September 25, 2014