US scientists have unravelled the genetic code of all known strains of the common cold virus; by completing their diverse genomic sequences they were able to map not only their RNA configurations but also determine their family trees to reveal how closely they may be related and what characteristics they may or may not share as a result of mutating through neighbouring or distant evolutionary branches. The results will provide a useful platform for researching and developing vaccines against the common cold, they said.
The study was the work of researcher at the University of Maryland School of Medicine in Baltimore and colleagues at the University of Wisconsin-Madison, and is published online before print in the 12 February issue of Science.
The authors wrote that human rhinoviruses (HRVs) are a major cause of diseases in the upper and lower respiratory tract of humans worldwide and there are many different phenotypes or strains.
Senior author, Dr Stephen B Liggett, professor of medicine and physiology at the University of Maryland School of Medicine and director of its Cardiopulmonary Genomics Program, said in a separate statement:
“There has been no success in developing effective drugs to cure the common cold, which we believe is due to incomplete information about the genetic composition of all these strains.”
Liggett, who is a pulmonologist and molecular geneticist, said that we tend to think of colds as more of a nuisance than anything, but they can be risky for the very young and the elderly, and can trigger asthma attacks at any age.
“Also, recent studies indicate that early rhinovirus infection in children can program their immune system to develop asthma by adolescence,” said Liggett.
Liggett and colleagues discovered that human rhinoviruses that cause the common cold are organized in about 15 family groups, each with its own ancestral path, which may explain why no one anti-viral drug works against all of them.
“Perhaps several anti-viral drugs could be developed, targeted to specific genetic regions of certain groups,” explained Liggett, adding that, “the choice of which drug to prescribe would be based on the genetic characteristics of a patient’s rhinovirus infection.”
Liggett said that while anti-virals may be the best option, their data also suggests that vaccines might be an effective route as well, particularly as they get more and more samples from patients and can quickly sequence the whole genome of the viruses and see how often they mutate in one season. He said that kind of work was already taking place, suggesting that vaccine development for the common cold (notorious for frequent mutation) may not be as difficult as people might think.
Co-investigator Dr Claire M Fraser-Liggett, director of the Institute for Genome Sciences and professor of medicine and microbiology at the University of Maryland School of Medicine, spoke of what she described as a “new insight” discovered by the study: that the human rhinovirus takes a shortcut when it starts making protein in the host cell, it skips a step, and this may explain why people feel ill so soon after becoming infected.
“We would not have had any sort of intuition about this had it not been revealed through genome analysis,” said Fraser-Liggett.
“Information that comes from this discovery might present a completely different approach in terms of therapy,” she added.
The researchers also discovered that human rhinoviruses are capable of doing something not thought possible in that type of virus: they recombine to form new strains. Two different strains can infect the same person and exchange material to form a third strain, known as a recombination, which may account for the speed with which new strains emerge within one season.
They found as many as 800 new mutations in virus samples taken from patients with colds, which they compared to older strains. Liggett said they found mutations in all parts of the genome.
Lead author, Dr Ann C Palmenberg, professor of biochemistry and chair of the Institute for Molecular Virology at the University of Wisconsin-Madison, said:
“As we begin to accumulate additional samples from a large number of patients, it is likely that hotspots for mutation or recombination will become apparent, and other regions resistant to mutational change may emerge.”
This will help scientists work out how flexible the virus is in response to changes in its environment, which is valuable information for therapy developers.
Before this study, scientists had only mapped a few dozen rhinovirus genomes, but as work began, other scientists came forward with new maps, so that the collection began to expand to a size bigger than was first thought. As Fraser-Liggett explained:
“It was clear to us that the spectrum of rhinoviruses out there was probably much greater than we realized.”
She said they realized they needed to develop a framework to study ways of combating the viruses and use their genetic signatures to predict how they might affect the people they infect.
The researchers modeled and compared each sequence to each other, so that they now have enough pieces of the jigsaw to be able to answer questions like how the rhinoviruses might mutate as they spread from host to host; which ones are more closely linked to asthma; and which ones might cause asthma later in life when exposed to in infancy.
“With all this information at hand, we see strong potential for the development of the long-sought cure for the common cold, using modern genomic and molecular techniques,” said Fraser-Liggett.
New DNA sequencing tools means that researchers can look at whole genomes much more quickly, and “answer multiple questions in parallel”, she added.
“Sequencing and Analyses of All Known Human Rhinovirus Genomes Reveals Structure and Evolution.”
Palmenberg AC, Spiro D, Kuzmickas R, Wang S, Djikeng A, Rathe JA, Fraser-Liggett CM, Liggett SB.
Science,Published Online February 12, 2009
DOI: 10.1126/science.1165557
Sources: Journal abstract, University of Maryland Medical Center.
Written by: Catharine Paddock, PhD