Grace Chua Straits Times 22 Dec 12;
BATS harbour viruses that can infect and even kill humans and animals, like Sars, Hendra and Nipah. Yet infected bats rarely fall sick.
Now, a Singapore-led team of international scientists has worked out a possible reason and believes it could help stop viruses leaping to humans and other animals.
The findings could even help to treat viral illnesses.
The key lies in bat genes. In July, the researchers started sequencing the genomes - the whole set of genes - of two very different bats.
One was a large fruit bat, a member of a group called megachiroptera. The other was a small insect-eating one belonging to a group called microchiroptera.
As these species are so different, any genes they share come from the last common ancestor of both bats.
Professor Wang Linfa, director of the Duke-NUS graduate medical school's Emerging Infectious Diseases Programme, led the team, which studied which genes had been selected most successfully during evolution.
Bats are the only flying mammals, and flight takes a great deal of their energy. The higher metabolic rates that supply this energy also produce toxic by-products that damage DNA. But bats seem to have evolved ways to protect their cells against this damage, Prof Wang explained. These DNA-repair genes also play a role in immune pathways, so researchers think they may help to protect bats.
A group of genes involved in inflammation was completely absent in bats. Inflammation is the body's response to an invader, such as a virus, resulting in viral illness.
Said Prof Wang: "We don't want to jump to conclusions that this means bats have less inflammation during viral infection. It's only one discovery and we have to do more to functionally prove that it contributes to less pathology in viral infection in bats."
But simply responding less to viruses could be part of why bats do not fall ill, he said.
Prof Wang led an international team spanning Singapore, China, Denmark and the US. Its work, published yesterday in the journal Science, may one day help prevent transmission of these viruses. It may point to better ways to treat viral diseases by using gene therapy, for example, to control inflammation, Prof Wang said.
National University of Singapore evolutionary biologist Rudolf Meier, who was not involved in the study, said some changes in the bat genes were present in other species, including humans, but without the protective DNA-repair or immune-system effects. He said the results were not wrong, but not conclusive.
Bats' viral immunity linked to their ability to fly
Heng Wei Xiang Today Online 22 Dec 12;
SINGAPORE - The evolution of flight in bats may has contributed to the development of a highly effective immune system, allowing these mammals to harbour some of the world's deadliest viruses such as Ebola and SARS.
This is according to researchers at Duke-NUS Graduate Medical School, who published their findings in the international journal Science. Less than 10 per cent of research papers submitted to the journal are published.
Professor Wang Lin Fa, an infectious disease expert who led the study, hopes the findings could provide new research directions, especially in the treatment, prevention and control of emerging infectious diseases that affect both humans and livestock.
The researchers studied two bat species, the black flying fox and the mouse-eared bat. While a high metabolism is a prerequisite for bats to be able to fly, such metabolic rates also increase the amount of free radicals present within cells in the bat's body. Excessive amounts of free radicals lead to DNA damage, contributing to major bodily disorders. Researchers found gene variants in these bat species, enabling them to minimise and repair DNA damage.
However, the same gene variants also boost bats' immune systems, allowing them to resist many viruses such as Nipah, Ebola and SARS, which typically cause severe illness in other species, humans included.
"Our findings highlight the potential of using bats as a model system to study infection control, tumour biology, and the mechanisms of ageing," said Prof Wang, who was appointed Director of the Program in Emerging Infectious Diseases at Duke-NUS in July this year.
Long-lived bats offer clues on diseases, aging
Tan Ee Lyn Reuters Yahoo News 21 Dec 12;
HONG KONG (Reuters) - The bat, a reservoir for viruses like Ebola, SARS and Nipah, has for decades stumped scientists trying to figure out how it is immune to many deadly bugs but a recent study into its genes may finally shed some light, scientists said on Friday.
Studying the DNA of two distant bat species, the scientists discovered how genes dealing with the bats' immune system had undergone the most rapid change.
This may explain why they are relatively free of disease and live exceptionally long lives compared with other mammals of similar size, such as the rat, said Professor Lin-Fa Wang, an infectious disease expert at the Duke-NUS Graduate Medical School in Singapore who led the multi-centre study.
"We are not saying bats never get sick or never get infections. What we are saying is they handle infections a lot better," Wang said in a telephone interview.
What was missing from both species of bats was a gene segment known to trigger extreme, and potentially fatal, immune reactions to infections, called the cytokine storm.
Cytokine storms end up killing not only offending viruses in the body, but the host's own cells and tissues too.
"Viruses rarely kill the host. The killing comes from the host's immune response. So it looks like what bats are doing is depress the inflammation (cytokine storm). If we can learn that, we can design drugs to minimize the inflammation damage and control viral infection," Wang said.
The study, which saw the participation of researchers from China, Denmark, Australia and the United States, was published on Friday in the journal Science.
Compared with other mammals of similar size, bats live a long time, with lifespans of between 20 and 40 years. Rats live between 2 and 3 years, on average.
IMMUNE GENES LINKED TO FLIGHT
Interestingly, Wang and his colleagues found that the highly evolved genes that give bats their superior immune system also enable them to fly.
Out of more than 5,000 types of mammals on the planet, bats are the only one capable of sustained flight and some species can fly more than 1,000 km in a single night.
Such intense physical exertion is known to produce toxic "free radicals" that cause tissue damage and it is these same genes that give the bat the ability to repair itself, Wang said.
"What we found was the genes that evolved fastest were genes involved in repairing DNA damage. That makes sense ... because when you fly, metabolism goes up and it generates free radicals that are toxic to cells," Wang said.
"Because bats fly, they (would have had) to evolve and adapt ... to get genes that can repair DNA damage."
Wang said we have much to learn from the bat, which has evolved to avoid disease and live exceptionally long lives.
"Cancer, ageing and infectious disease, these are the three major areas of concern for people," he said.
"We have studied rats for 150 years to understand how to do better in these three areas. Now we have a system, the bat, that has done very well in evolution. We can learn from the bat. With modern techniques, we can design new drugs to slow down the ageing process, treat cancer, fight infections."
(Editing by Robert Birsel)
Bats' flight linked to immunity
Duke NUS Science Alert 7 Jan 13;
An international team led by an infectious disease expert, Professor Lin-Fa Wang, at the Duke-NUS Graduate Medical School (Duke-NUS) in Singapore has found that the evolution of flight in bats may have contributed to the development of a highly effective immune system, allowing bats to harbour some of the world’s deadliest viruses such as Ebola and SARS.
In their study, published in the prestigious international journal Science, Professor Wang and colleagues used a state-of-the-art whole-genome sequencing technique to analyse the genomes of two distantly-related bat species, the fruit bat Pteropus alecto (Black flying fox, a species native to Australia, Papua New Guinea, and Indonesia) and the insect-eating bat Myotis davidii (David's mouse-eared bat, a species endemic in China).
"This is the first in-depth study of bat genomes. Our study provided important genomics insights into the unique biological features of bats," said Professor Wang, an expert in bat-borne viruses who was appointed Director of the Program in Emerging Infectious Diseases at Duke-NUS in July this year.
The large collaborative team from China, Denmark, Australia, U.S., and Singapore compared the two bat genomes with the genomes of other mammals, and found genetic clues that may account for the unique characteristics of bats.
Although bats are the second largest group of mammals, with over 1,000 species of bats documented so far, they are distinctive because they are the only mammals capable of sustained flight; other mammals such as flying squirrels glide but do not fly.
Previous research has shown that this ability to fly may be linked to high metabolic rates in bats. However, increased metabolism also elevates the amount of free radicals in living cells, resulting in DNA damage that is harmful to the bats.
Through their analysis of bat genomes, the researchers have now solved the mystery of how bats tolerate high levels of free radicals. It appears that bats have evolved mechanisms to overcome this toxic side-effect of flying, as they possess gene variants that help them minimise and repair DNA damage.
And here is where bats' ability to fly and their immunity against viruses intersect: the same gene variants that minimise DNA damage in bats may also provide protection against viruses, boosting their innate immune system to ward off such attacks.
Having a highly active immune system may explain why bats are natural hosts of many viruses such as Hendra, Nipah, Ebola, and SARS, yet rarely show any signs of infection. In contrast, when these viruses are transmitted to humans or other animals, the resulting illness is often severe and even fatal.
Bats are also known for their exceptional longevity which is unusual because of their small size and high metabolic rate. The researchers raise the intriguing possibility that the same mechanisms underlying the evolution of flight and viral immunity in bats may also be responsible for their life expectancy, although further research is required to establish this link.
Professor Wang hopes that the findings from this study will provide new research directions into infectious diseases, especially in the treatment, prevention, and control of emerging infectious diseases that affect both humans and livestock animals.
"Our findings highlight the potential of using bats as a model system to study infection control, tumour biology, and the mechanisms of ageing," said Professor Wang, who intends to continue studying bat-borne viruses in Duke-NUS, tapping on Duke-NUS' strengths in human infectious disease research for viral diseases such as dengue and influenza, and to explore new collaborative research in tumour biology with scientists in the Cancer and Stem Cell Biology Program at Duke-NUS.
Professor Wang is also a Science Leader for the CSIRO Office of the Chief Executive and Senior Principal Research Scientist at the CSIRO Australian Animal Health Laboratory (AAHL) in Geelong, Australia.
