Biologia Molecular

“A person can become infected with two viruses, and a third unique virus is formed.”
–Dr. Stephen B. Liggett

By Val Willingham, CNN Medical Producer

(CNN) — A cure for the common cold has eluded scientists since the dawn of mankind.

Common colds — also known as human rhinovirus — affect billions of people worldwide every year and have more than 100 different, but related, strains. Each of these strains can cause a variety of symptoms in sufferers.

Doctors say that variety is what makes the common cold so hard to understand and so hard to treat.

Last year, researchers from the University of Maryland and the University of Wisconsin-Madison announced that they had taken the first step in finding a cure for rhinovirus by mapping each strain’s entire genome.

Now, those same scientists have found some interesting things about all those different strains.

“We continue to see a new virus that appears to come from two viruses,” said Dr. Stephen B. Liggett, co-leader of the project and a professor of medicine and physiology at the University of Maryland School of Medicine. “So a person can become infected with two viruses, and a third unique virus is formed.”

Why those mutations develop is still a major question, but Liggett says most of them don’t cause any harm. “It’s really more about why they develop … because many are not very strong, but in some cases, they are,” he said. “So we need to better understand them.”

A person can become infected with two viruses, and a third unique virus is formed.

–Dr. Stephen B. Liggett
When the different strains of the common cold were mapped early last year, researchers were looking for ways to develop diagnostic tests and eventually possible treatments.

Since the completion of the mapping, researchers have been working on a diagnostic test for the virus.

Originally, the test was expected to cost about $2,000, but they have perfected the technique and found they can develop a much cheaper test for about $20. That means a test for the cold may one day be common in doctors’ offices.

A fast and inexpensive test is good news for asthmatics and people who have chronic obstructive pulmonary disease, for whom colds can be life-threatening.

“Fifty percent of the exacerbations that occur in patients who have these two diseases are due to a rhinovirus infection,” Liggett notes. “So it’s that group of people we are targeting. Those would be the first group we’d like to help.”

Respiratory infections including colds and the flu are some of the most common causes of asthma flare-ups, especially in young children, according to the American Asthma Foundation.

Although the genetic mapping of the different strains is a positive step, many in the medical community say the virus itself is just too complex to tackle.

But Liggett ignores the naysayers; he says that by mapping the genome of the different strains and assembling the results into a “family tree,” scientists can better understand how virus strains are related, as well as their differences.

Last year, researchers found that human rhinovirus strains are organized into about 15 subgroups, so a “one-drug-fits-all” approach to treat the cold probably won’t work.

But Liggett says he and his fellow researchers hope to streamline those 15 subgroups into five, which would make it easier to treat the virus. “Better to have five treatments than 15,” Liggett said.

“Right now, vaccines and other treatments aren’t our main goal,” Liggett said. “Hopefully, we will be able to design treatments some day. Taking our research little by little will help us understand a virus we’ve never been able to figure out before. And for now, that’s what’s most important.”

NEW YORK (GenomeWeb News)

January 06, 2010
By a GenomeWeb staff reporter

An international research team has garnered evidence that bits of non-retroviral RNA viral elements have made their way into mammalian genomes.

A Japanese and American research team searched through mammalian and other sequence databases for sequences resembling the non-retroviral RNA bornaviruses. Indeed, their search turned up endogenous Borna-like N elements, which they dubbed EBLN elements, in the human genome and genomes of other animals including non-human primates, rodents, and the elephant.

The research, which appeared online today in Nature, offer the first evidence of such non-retroviral sequence incorporation into mammalian genomes — and suggests bornaviruses infected some mammalian species tens of millions of years ago.

“Our results provide the first evidence for endogenization of non-retroviral virus-derived elements in mammalian genomes and give novel insights not only into generation of endogenous elements, but also into a role of bornavirus as a source of genetic novelty in its host,” senior author Keizo Tomonaga, a virology researcher affiliated with Osaka University and the Japan Science and Technology Agency, and colleagues wrote.

Mammalian genomes are known to contain viral sequences. But so far researchers have only found evidence of retroviral sequences in these genomes.

On the contrary, the new study suggests mammalian genomes also contain non-retroviral RNA from bornaviruses, a group of non-segmented, negative sense RNA viruses.

To find these sequences, the researchers first trolled human protein databases for sequences resembling those found in Borna disease viruses. That search yielded two hypothetical proteins with sequence similarity to the bornavirus structural protein nucleoprotein.

After finding these human homologues, the researchers looked for EBLN elements in other mammalian genomes using tblastn searches of NCBI eukaryote and whole-genome shotgun sequence databases and Southern blot hybridization experiments.

In the process, the team found EBLN orthologues in chimpanzee, gorilla, orangutan, macaque, and other primate genomes. Similar sequences also turned up datasets representing the African elephant, cape hyrax, and several rodent species.

In their subsequent experiments, the team started unraveling the phylogenetic relationships between the EBLNs. They also provided evidence supporting the notion that bornavirus sequences can be copied to DNA and incorporated into the genome.

The researchers’ findings suggest EBLN elements have been around in primate genomes for more than 40 million years. In contrast, these elements seem to have become incorporated much more recently in the genome of the thirteen-lined ground squirrel (the only squirrel species in which they found EBLN elements).

Although it’s still unclear exactly how these viral elements got into mammalian genomes, the researchers argue that sequence characteristics suggest retrotransposon related reverse transcriptase may have been involved.

And while most EBLNs seem to occur in pseudogenes, the team noted that some of the elements might have functional roles in their host mammalian genomes — a possibility that requires further exploration.

“This report is the first to provide evidence of endogenous sequences derived from a non-retroviral RNA virus in mammalian sequences,” the team wrote, adding that the findings imply that bornaviruses are the “first non-retroviral RNA virus whose existence in prehistoric times has been confirmed.”