Scientists Decode Entire HIV Genome
A team of US scientists has for the first time unravelled the entire genetic code of HIV, the virus that causes AIDS, paving the way for a better understanding of how these types of viruses infect humans and hopefully speeding up the discovery and development of new drugs.
The work was done by Dr Kevin Weeks, a chemistry professor of the College of Arts and Sciences at the University of North Carolina (UNC) at Chapel Hill, and colleagues, and features as the cover story of the 6 August issue of Nature.
Before this work, researchers had only modelled small regions of the HIV genome, which is very large and made of two strands of nearly 10,000 building blocks or nucleotides each.
Viruses like HIV, whose genetic code is carried on RNA (rather than DNA) are harder to unravel because unlike DNA where the code is carried almost entirely in sequential building blocks or nucleotides, RNA folds into complex and intricate three-dimensional patterns that are harder to unravel. Other RNA-based viruses include the flu viruses, hepatitis C, the common cold, some cancer precursors, polio, and many others.
The replication of RNA-based viruses is controlled at many levels, including conserved "structures" of RNA genome, many of which have not been studied in much detail.
The way the HIV encodes proteins is not straightforward either: while there is a correspondence between RNA and a primary sequencing of proteins, there is another level of coding between these "structures" and "inter-domain" loops that connect different parts of HIV proteins.
For the study, the researchers used a high-throughput RNA analyser called SHAPE to examine the architecture of HIV genomes isolated from infectious cultures containing trillions of viral particles.
What they found suggests that the complex RNA structures (which they referred to as "motifs") influenced several steps in the HIV infectivity cycle, in other words they modulated "ribosome elongation to promote native protein folding".
They also found that: "Some simple genome elements previously shown to be important, including the ribosomal gag-pol frameshift stem-loop, are components of larger RNA motifs."
"There is so much structure in the HIV RNA genome that it almost certainly plays a previously unappreciated role in the expression of the genetic code."
The study could be the key to unlocking the secrets of other RNA genomes in other viruses.
"One approach is to change the RNA sequence and see if the virus notices," said co-author Ronald Swanstrom, from UNC's Linenberger Cancer Center.
"If it doesn't grow as well when you disrupt the virus with mutations, then you know you've mutated or affected something that was important to the virus," he added.
And another important insight that Weeks pointed out was:
"We are also beginning to understand tricks the genome uses to help the virus escape detection by the human host."