An investigation through decades-old frozen infant stool samples seems to have surrendered rich dividends for researchers from the National Institute of Allergy and Infectious Diseases (NIAID). NIAID is known to be a part of the National Institutes of Health.
The team was believed to have modified a laboratory method in order to screen thousands of samples for norovirus. Apparently, norovirus is the main cause of acute gastroenteritis outbreaks in people of all ages. The researchers discovered that the rate of evolution of a specific group of noroviruses could possibly assist them in developing specific antiviral drugs. They also found a probable vaccine against a disease which appears to be very unpleasant and sometimes toxic.
Highly contagious, noroviruses are believed to be responsible for an immediate onset intestinal ailment also called winter vomiting disease or cruise-ship disease. The Centers for Disease Control and Prevention (CDC) estimates that approximately 23 million cases of acute gastroenteritis take place every year due to norovirus infection. Moreover, they seem to be the cause of more than half of all food borne gastroenteritis outbreaks.
In elderly people, infants and people with compromised immune system function, dehydration resulting from vomiting and diarrhea following norovirus infection could possibly be severe.
This research was noted to have been led by Kim Y. Green, Ph.D., and Karin Bok, Ph.D., of NIAID’s Laboratory of Infectious Diseases. Additionally, NIAID scientist Albert Z. Kapikian, M.D., is known to be a co-author on the paper.
In 1972, Dr. Kapikian along with his colleagues seemed to have identified and characterized the norovirus. Also, norovirus was noted to have been responsible for an outbreak of acute gastroenteritis in Norwalk, Ohio, in 1968.
“Thanks to the foresight of Dr. Kapikian and others at NIAID and the Children’s National Medical Center who established and have maintained these clinical samples since 1974, our researchers have a unique resource that represents one of the oldest sets of norovirus samples in the world. This is the first study to look at samples that date back almost to the first recorded cases of norovirus outbreaks, more than 40 years ago,” says NIAID Director Anthony S. Fauci, M.D.
According to a 2008 estimate by CDC researchers, nearly 200,000 children in developing countries who are less than 5 years old seem to die of norovirus infection each year. It was observed that there is no vaccine against norovirus and no specific antiviral drug to cure infections. Dr. Green explains that an important question for norovirus researchers is to determine when the dominant variant, called genotype II.4 (GII.4), first emerged.
“This genotype has been associated with the majority of global outbreaks of acute norovirus gastroenteritis since the mid-1990s. The GII.4 genotype was first described around 1987, but no one knew for sure whether that genotype emerged then or if it existed earlier,” continues Dr. Green.
In order to answer the question, Dr. Bok was noted to have customized a novel technique and applied it to stool samples which were initially collected from infants and young children hospitalized at the Children’s National Medical Center in Washington, D.C., between the year 1974 and 1991.This new technique was called as real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Additionally, samples were believed to have been collected from infants and children with gastroenteritis and from others who did not have gastroenteritis. Basically, Dr. Bok crafted genetic hooks which might have been capable of searching out matching genetic sequences of any norovirus present in the samples.
Dr. Bok discovered that about fifty out of 5,424 samples tested seemed to have contained norovirus. The most frequently seen genotype was GII.3 i.e. 48 percent, but the second most common genotype appears to have been GII.4 i.e. 16 percent. It was observed that some GII.4-containing specimens dated back to 1974. Apparently, this allowed the researchers to conclude that this now-dominant genotype had been circulating for years before its more recent discovery as the cause of severe global outbreaks of norovirus disease.
Subsequently, with the help of a strategy developed by NIAID scientist Stanislav Sosnovtsev, Ph.D., the researchers determined the complete genetic sequences of five older GII.4 viruses. Furthermore, they appear to have compared those sequences to gene sequences of current GII.4 noroviruses. The comparison allowed the investigators to determine how much the archival viruses appear to have varied from the most recent representatives of the same genotype. It also allowed them to calculate how quickly the GII.4 genotype seems to be evolving.
Researchers claimed that, at present, there are no antiviral drugs particularly targeted to noroviruses. However, the latest information about which segments of the norovirus genome seems to have changed the least could assist in the development of novel drugs. Supposedly, these new drugs could be targeted at those more hereditarily static portions of the virus.
Dr. Green was of the opinion that noroviruses, like influenza viruses seem to mutate readily and evolve rapidly. If vaccines against noroviruses become achievable in the future, researchers would perhaps need to take into consideration shifts in the virus’s genetic make-up and reformulate the vaccines in order to match the virus. However, unlike influenza viruses, noroviruses cannot possibly be grown in the lab thereby raising an extra problem to vaccine development.
“By examining the history of norovirus evolution contained within these archival samples, we can see how the virus has changed during this time, and we also can better predict how the virus is likely to change in the future,” says Dr. Bok.
“This research is the first to reveal the speed at which the molecular clock of norovirus runs,” continues Dr. Green.
Dr. Green along with her colleagues is at present analyzing stool samples from the 1960s in Dr. Kapikian’s collection. If norovirus could be detected in those samples, knowledge about the ancestry and rate of evolution of this virus may perhaps be further extended. Dr. Green claimed that if researchers one day crack the problem of growing norovirus in the lab, information about the rate of evolution could possibly be invaluable to develop vaccines.
The findings of the research will be published in the Journal of Virology.