Thursday, November 18, 2010

Off Topic: Animal genomes "The Roots Of A Virus"

Hepatitis B Virus

Also See :The Origin Of Hepatitis

.I am virus – animal genomes contain more fossil viruses than ever expected

.If you think about fossils, you probably picture a piece of bone or shell, turned to stone and buried in the ground. You visit them in museums; some of you may even have found some. But your closest fossils are inside you, scattered throughout your genome. They are the remains of ancient viruses, which shoved their genes among those of our ancestors. There they remained, turning into genetic fossils that still lurk in our genomes to this day.
We’ve known about our viral ancestors for 40 years, but a new study shows that their genetic infiltration was far more extensive than anyone had realised. The viral roots of our family tree have just become a lot bigger.

When viral genes were first found among animal genomes in the 1970s, all of them came from the retroviruses, a group that includes HIV. As part of their life cycle, these viruses smuggle themselves into the genomes of the cells they infect, making new copies of themselves using their host’s own machinery. These copies usually cut themselves back out to form new virus particles but sometimes, they stayed behind. Some were passed down through the generations and became permanent parts of their host’s genome. Today, these “endogenous retroviruses“, or ERVs, make up around 8% of all our DNA.

But the retroviruses weren’t alone. Scientists have recently discovered that other viral dynasties have also become genomic trespassers. In 2009, French scientists found that some wasps have accosted the DNA of polydnaviruses for use as biological weapons. In January this year, a Japanese team announced that another family – the bornaviruses – have penetrated the genomes of animals, including humans. In the summer, American teams showed that the same was true for filoviruses, such as the lethal Ebola and Marburg. Just last month, fragments of hepatitis-like viruses were found hiding out in the genes of the zebra finch.

Now it seems that even these discoveries were just the tip of the iceberg. Aris Katzourakis and Robert Gifford have found that the animal kingdom is rife with viral genes. By screening the entire genomes of 44 species, they found fossils representing ten other families beyond the retroviruses. Some of these ancient viruses are relatives of today’s most infamous varieties: influenza, Ebola, hepatitis B, rabies, dengue and yellow fevers, and more. The term ERV is clearly too narrow, so Katzourakis and Gifford describes these genetic fossils by the more inclusive name of “endogenous viral elements” or EVEs.

Hiv Virus

Most of them are broken and fragmented. Riddled with crippling mutations, they are like books whose pages have been smudged, torn out and written over. But not all – some seem intact, and their information can still be read today. One of these, known as EBLN-1, is found in humans and other primates. It came from an ancient bornavirus and its slow pace of evolution means that we’ve probably co-opted it into our own genomes, recruiting it into an active role.

It’s not clear what that role might be, but Katzourakis and Gifford think that it might help to protect us against its own kind. Other groups have suggested that this is a common theme – the fossil viruses become recruited as sentinels that fights off invasions by their live cousins. If that’s the case, you’d expect the live viruses to eventually evolve countermeasures. When this happens, the EVEs become useless, the benefits of keeping them intact dwindle, and mutations start to build up. And that’s exactly what you see with EBLN-1 – in animals like orang-utans and marmosets, it has started to lose its integrity.

While a minority of EVEs have an active physical role, the sequences as a whole have much to tell us about the evolution of viruses themselves. EVEs are windows into the past, just as all fossils are. As an example, step away from viruses for a minute and consider whales. it’s difficult to imagine how whales evolved from land-based ancestors by comparing modern species, all of which share the same set of advanced sea-going adaptations. However, a stunning series of fossil whales makes the gradual transition from land to sea that much clearer.

It’s even more difficult to understand the history of viruses by looking at modern ones, because they evolve at a lightning pace, switching hosts, shuffling genes and even losing entire lineages. The EVEs provide a glimpse into these lost events, telling us how old viruses are, which hosts they used to infect, and even how they were transmitted.

When EVEs were first introduced into an animal’s genome, they became dragged along for the ride as that species evolved. Today, the host’s descendants all carry similar EVEs. Those similarities provide an important historical clue – they tell us that the last common ancestor of species with related EVEs must have had the viral DNA in its genome. By working out when that ancestor was around, we can work out how old the group of viruses are. With enough data, you could even piece together the genomes of the ancient viruses themselves. As a commenter said, the last time I wrote about this, “Then we can say want kind of genome the flu had which infected T. rex. That would be totally awesome.”

Take the bornaviruses. When they were found in animal genomes earlier this year, it was clear that those in our genome had been hitching a ride in animal bodies for 40 million years. But Katzourakis and Gifford’s study shows that this group is much older than that. Based on closely related EVEs from elephants and tenrecs (a hedgehog-like creature), bornaviruses have been around when the last common ancestor of elephants and tenrecs were – and that’s at least 93 million years ago.

EVEs can also tell us about the hosts of ancient viruses. Today, filoviruses like Ebola are thought to infect bats and primates. Last year, one strain was discovered in Philippine pigs. But the tell-tale EVEs show that these viruses also used to infect insect-eaters like shrews, rodents like mice and rats, and marsupials like wallabies and opossums. They certainly used to have catholic tastes in hosts, and they still might do. In this way, EVEs could tell us about modern animals that could act as reservoirs for notable deadly viruses.


Ebola Virus

They can also tell us about viruses that jumped from one animal to another. Katzourakis and Gifford found an EVE in the genome of the bottlenose dolphin that seems to be very closely related to dependoviruses that infect birds, like chickens and ducks. This doesn’t mean that a duck infected a dolphin; remember that EVEs are fossils of infections that plagued the distant ancestors of current species. However, it does strongly suggest that in prehistoric times, one such virus jumped from birds to mammals, as often happens today.

Reference: PLoS Genetics
Update: More unabashed joy at this discovery from Carl Zimmer. Look out for his upcoming book on viruses.

***Note (From July 12, 2010)

Newly Discovered Hepatitis C-Related Virus Found in Bats

Wildlife Trust Scientist Employs Advanced Genetic Sequencing to Uncover New Pathogen
NEW YORK, July 12 /PRNewswire-USNewswire/

Wildlife Trust, the global conservation health organization, announced the discovery of a previously unknown pathogen that may offer insight into the origins of the Hepatitis C virus. The virus, tentatively named GBV-D, is related to a group of GB viruses, previously only known to occur in monkeys and humans. Dr. Jonathan Epstein, Associate Vice President of Conservation Medicine Programs at Wildlife Trust, reveals in a paper published in PLoS Pathogens that the new viral discovery is part of a large family of viruses, called Flaviviridae, which includes the Hepatitis C virus, GB viruses and others. Viral hepatitis affects more than 500 million people worldwide and is the leading cause of liver failure and liver cancer.
Wildlife Trust scientists are actively surveying wildlife species, such as bats, for viruses that may threaten human health in key regions all over the world that are highly vulnerable to disease emergence. The team was actively testing bats for the deadly Nipah virus that infects and kills people each year in Bangladesh. It is estimated that infectious diseases lead to 13 million human fatalities per year. Additionally, over three-quarters of emerging infectious diseases are a result of zoonotic pathogens.

Bangladesh is a notable emerging disease hot spot due to its dense population and the close association between wildlife and humans. Scientists tested 100 giant fruit bats, Pteropus giganteus, in the Faridpur region of the country. "Bangladesh is densely populated and large colonies of bats roost in close proximity to people. We know from studying Nipah virus that bat viruses can be transmitted to people through food-borne pathways," said Dr. Jonathan Epstein.
Bats are known to be the reservoir for many zoonotic viruses including rabies, Ebola, Marburg, Hendra, Nipah, and SARS. Wildlife Trust is working to predict and prevent emerging diseases by actively testing wildlife in critical hot spots around the world. "The Indian subcontinent and South Asia are areas where we are ardently working to identify the next possible pandemic disease," stated Dr. Peter Daszak, President of Wildlife Trust.

In the lab, the bat blood samples were analyzed using high-throughput pyrosequencing – an emerging platform for DNA analysis. The technology has helped scientists improve genomic sequencing and enabled Dr. Epstein to discover the new GBV-D virus. "It's essential to understand if and how viruses are being transmitted from animals to people in an outbreak setting such as SARS, but it's equally important to identify the natural reservoir of the virus, which may not be directly infecting people, to ensure that more outbreaks don't happen in the future," said Dr. Epstein. "With our preliminary research it's too early to tell if GBV-D could cause disease in human populations. Our next steps will require testing people that come in contact with these bats to gauge possible infections."

Available Topic Expert(s): For information on the listed expert(s), click appropriate link.
Peter Daszak
Jonathan Epstein
SOURCE Wildlife Trust



References and additional links from :

I am virus – animal genomes contain more fossil viruses than ever expected

.More on fossil viruses:

Meet your viral ancestors – how bornaviruses have been infiltrating our genomes for 40 million years

Wasps use genes stolen from ancient viruses to make biological weapons

The viruses that have been infecting mammals for 105 million years

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