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Thursday, February 12, 2009

Complete Genomes of All Known Human Rhinoviruses are Published; Rhinoviruses Are Associated With Common Cold

A team of researchers from the J. Craig Venter Institute (JCVI); the University of Maryland School of Medicine and the University of Wisconsin, Madison; announced today they have sequenced and analyzed the genomes of all known human rhinoviruses (HRVs). The whose work was published in Science Express, the online edition of the journal Science.

Rhinoviruses, part of the Picornaviridae family, are immediately familiar as the cause of the common cold, but they are also responsible for acute lower respiratory symptoms, and are a major cause of emergency room visits for patients suffering from asthma and chronic obstructive pulmonary disease (COPD). The direct and indirect cost of treating these illnesses is billions of dollars yearly, thus finding new ways to treat and perhaps prevent these illnesses could substantially cut health care costs.

Rhinoviruses are traditionally divided into two groups, HRV-A and HRV-B, consisting of 99 viral serotypes. The extraordinary genetic diversity of circulating rhinovirus serotypes has prevented the production of a universal vaccine for the common cold. A recently discovered third group of rhinoviruses, HRV-C, has swept the globe causing severe lower respiratory symptoms in patients.

To better understand the biology, diversity and evolution of human rhinoviruses, the researchers in this study sequenced and analyzed the genomes of all known HRV-A and B reference strains, as well as 10 new field isolates. The whole genome sequencing and bioinformatic analyses on the rhinovirus evolution were conducted at JCVI.

By constructing a rigorous phylogeny of all complete HRV genomes, the team gained new insight into rhinovirus evolution. They clearly showed that HRV-A and HRV-C evolved from a common ancestor and that HRV-B is "sister" group to the other two species. Interestingly, the team also uncovered within the HRV-A strain what they believe could be a separate, distinct fourth HRV subgroup.

The authors demonstrated in this study that recombination, the exchange of genetic information by breaking and rejoining nucleic acid sequences, is a common evolutionary mechanism in rhinoviruses. Co-infection with multiple viruses in individual patients can lead to the generation of novel rhinovirus serotypes. The authors also saw a high rate of diversity among field samples of the same HRV serotypes in the same geographic area over a short time period, suggesting that rhinoviruses may escape antiviral drugs through rapid mutation.

The researchers also found several areas of interest in the HRV genomes which could help to better understand the infection mechanism. Specifically, nearly all the HRVs displayed a hypervariable region in the 5'UTR. In the poliovirus a similar region is found which determines the virulence of that virus, suggesting that this genomic region could determine the pathogenicity of individual HRV strains.

According to researchers this study provides the scientific community with an extremely valuable resource for studying viral evolution. One researcher on the team says, "It is a very exciting time in viral genomics. Next generation sequencing technology will allow researchers to study as never before the evolution of viral populations worldwide. The completion of the HRV reference data set will open the door to mass comparative studies of rhinovirus evolution and global migration patterns."

Further full genome analysis with potentially thousands of additional field strains should enable even better understanding of these viruses leading to improved antivirals and vaccines.

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Friday, October 03, 2008

Smoking, Fuel Use in China Projected to Cause Millions of Deaths

If current levels of smoking and biomass and coal fuel use in homes continues, between 2003 and 2033 there will be an estimated 65 million deaths from chronic obstructive pulmonary disease (COPD) and 18 million deaths from lung cancer in China, accounting for 19 percent and 5 percent of all deaths in that country during this period.

Researchers at the Harvard School of Public Health (HSPH) predict that the combined effects of these two major factors alone will be responsible for more than 80% of COPD deaths and 75 percent of lung cancer deaths in China over a 30-year period. But interventions to reduce smoking and household use of biomass fuels and coal for cooking and heating could significantly reduce the number of deaths.

The findings are from a study that will appear online on October 4 and in the October 25 print issue of The Lancet. It is the first quantitative analysis to look at the combined effects of smoking and household fuel use on COPD, lung cancer and tuberculosis (TB).

Respiratory diseases are among the 10 leading causes of deaths in China. About half of Chinese men smoke and in more than 70 percent of homes in China residents cook and heat their homes with wood, coal and crop residues. Smoking and pollution from indoor burning of these fuels are major risk factors for COPD and lung cancer and have been linked with tuberculosis (TB). Globally, more than 900 million of the world's 1.1 billion smokers currently live in low-income and middle-income countries and about one half of the world's population uses biomass fuels and coal for household energy.

Using data on smoking, fuel use and current as well as projected levels of COPD, lung cancer and TB, the authors set out to estimate the effects of modifying smoking and fuel use on future COPD and lung cancer deaths and TB incidence. They grouped the results into scenarios based on whether interventions involved moderate control of smoking and fuel use, aggressive control or a complete cessation of exposures to the pollutants.

They found that reducing those two risk factors would significantly decrease deaths from COPD and lung cancer. If smoking and biomass and coal use were to be eliminated gradually over the next 30 years, an estimated 26 million COPD deaths (40 percent of projected COPD deaths) and 6 million lung cancer deaths (34 percent of projected lung cancer deaths) would be avoided. For moderate and aggressive control scenarios, deaths from these diseases could be reduced by an estimated 17 percent to 34 percent among men and 18 percent to 29 percent among women. There will also be major benefits for TB, above and beyond those that can be achieved through treatment.

Hsien-Ho Lin, a graduate student in the department of epidemiology at HSPH and the lead author of the study, says "this analysis shows that smoking and fuel use, which affects hundreds of millions of people in China, will be a defining feature of future health in that country."

Policy responses and specific interventions could help reduce the enormous disease burden from smoking and household fuel use. In the article, the authors suggest that at the national level, for example, authorities could create regulatory and economic policies that reduce smoking and promote clean household fuels. At the individual level, TB patients could be offered tobacco cessation programs.

"There are proven ways to reduce tobacco smoking and to provide homes with clean-burning energy alternatives. China can save millions of premature deaths from respiratory diseases in the next few decades if it leverages its effective policy system to implement these interventions," says Majid Ezzati, associate professor of international health at HSPH and senior author of the study.

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