HIV-1 elicits RNA silencing in human cells, but it also contains a sequence that suppresses the process, according to researchers at the National Institute of Allergy and Infectious Diseases. "Nucleic acid-based immunity in mammalian cells has been found before, but to date, there has been no single report of a natural small interfering RNA [siRNA] that is triggered by HIV in human cells," says coauthor Kuan-Teh Jeang. He adds that the virus' "counter strategy" is also unprecedented.
Jeang, Yamina Bennasser, and colleagues characterized a sequence in the HIV-1 genome that encodes a rare siRNA precursor: a short hairpin RNA (shRNA) that is processed by the Dicer (or by a Dicer-like) ribonuclease into siRNAs. In addition, they found that the virus prevents RNA silencing through a suppressor present in its Tat protein, which interferes with Dicer's activity.
"It's ... a very intriguing story," says Mario Stevenson of the University of Massachusetts. "A number of groups, including ours, have looked at the question of whether HIV encodes RNAs that can form siRNAs. Jeang's group was able to reveal that it does, before anyone else." Stevenson is interested in whether shRNAs can be effectively used against HIV as a suppressor mechanism. "If Jeang's results prove to be right, then the shRNA's therapeutic approach [which expresses an HIV-specific shRNA to be processed by Dicer into an antiviral form] may not be optimal."