Posted on 07/18/2006 6:27:06 PM PDT by blam
Is this the oldest human virus?
(Filed: 18/07/2006)
The papillomavirus has been afflicting humans and their ancestors for millions of years. Now scientists have worked out how it has evolved, reports Roger Highfield
Hundreds of millions of years ago, a relative of this virus made dinosaurs sprout warts. When our ancestors split from the apes up to seven million years ago, the virus split with them. Among the earliest modern humans, it was still multiplying, spreading and evolving.
Today, this virus, perhaps the oldest to afflict humankind, is causing more suffering than at any time in its history. Although many kinds of the virus - the human papillomavirus or HPV - still cause warts, certain types are now known to cause cervical cancer, too, an idea first suggested three decades ago by the German scientist Harald zur Hausen.
The cancer was documented as long ago as the second century AD by the Greek gynaecologist Soranus of Ephesus, but the death rate has risen because women are living longer, giving more time and opportunity for infection with the virus to trigger cancer. In recent years, however, modern genetics has helped scientists to track down the remarkably ancient origins of this invisible killer and provided the means to fight it.
Scientists can compare the genetic material in viruses to draw up a family tree. There are more than 100 types of HPV and they all consist of nothing more than a scrap of genetic material - DNA - wrapped in a spherical shell of proteins some 55 billionths of a metre across (around 1,500 would fit across a human hair).
About 40 are known to infect the genital tract and, of these, 13 HPV types have implicated in the development of cervical cancer: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 66. But of all these, the most important are types 16 and 18, which together are responsible for approximately 70 per cent of cervical cancers. Viruses multiply by pirating the molecular machinery of a host and it seems that, by doing this, these HPV strains can switch off the protein product of the p53 gene, one of the body's most important cancer defence genes, along with that of the retinoblastoma gene, which also suppresses tumour growth.
Over a lifetime, it is estimated that up to 80 per cent of sexually active women will be infected at some time or another. For the majority, the virus is quickly cleared by the immune system. Unfortunately it is not possible to predict who will not deal with infection and be left vulnerable to cervical cancer.
By studying the genetic make-up of the 100 or so HPVs, it has been possible to see the virus change down the generations. By making assumptions about how quickly they mutate, one can even work out when each type emerged. Only a few weeks ago, an international team used this approach to work out how the epidemic of HIV-1 - which has caused Aids in tens of millions of people - began with a person infected by chimpanzees in south-east Cameroon in the 1930s.
In a similar way, Prof Hans-Ulrich Bernard, from the University of California, Irvine, has used genetic genealogy to study the evolutionary history of HPV and shown how this family of viruses evolved together with humankind. "Homo sapiens was never without HPVs, and consequently never without warts and cervical cancer," he says.
HPV is amazingly ancient. While HIV jumped from animals to humans in the last century, and the viruses that cause smallpox and measles made the leap around 1,500 years ago, Prof Bernard found evidence that the HPVs have evolved over hundreds of thousands of years, probably longer.
In a study conducted with Drs Shih-Yen Chan and Lisa Ho of the National University of Singapore, Prof Bernard looked at 301 samples of HPV 16 from 25 different ethnic groups, including Eskimos from Greenland, South American Indians, and people from Finland, India, Israel, Japan, Greece, South Africa, Zaire, Sierra Leone, Senegal, New York, Peru and Argentina.
There were 48 different variants of HPV 16. In all they differed by just five per cent in terms of genetic code, showing a very slow evolutionary change. The team concluded that the infection was born in Africa, not least because ape and monkey papillomaviruses were so similar.
This picture was confirmed by Dr Chi-Keong Ong in Singapore who studied HPV 18. Working with colleagues from around the world, including Prof Saveria Campo of Glasgow University, he compared samples from Scotland, Germany, Greece, Tanzania, Singapore, Japan and Brazil. Two of the Brazilian samples came from an isolated tribe, the Mundurukú, who live in remote areas along the Cururu River.
The analysis shows an HPV 18 variant from Africa is the founder virus, and is by far the oldest, since its modern African descendants are the most varied. Although some strains in Brazil resulted from the colonisation by the Portuguese and Spanish, then the importation of slaves from Africa, the strains in the Mundurukú are different, suggesting that they inherited the virus carried by the original settlers of that region.
The diversity of HPV 18 has probably emerged over 200,000 years, shadowing the "out of Africa" diaspora of early humans. While agreeing with this conclusion, a review by Dr Aaron Halpern, of the University of New Mexico, went further: HPV might have been present seven million years ago, as human and chimpanzee species diverged.
So where did this ancestor of ape and man get the virus from? The analysis of HPV 16 suggested that the virus is at least 240,000 years old - and possibly as much as 24 million years old. "Interestingly this range brackets the estimated period of primate and human evolution," added Dr Chan and his colleagues.
But primates are far from the only creatures to be infected. There is an extraordinary range of wart viruses. Papillomaviruses infect just about every mammal - and some birds. There's one papillomavirus that infects chaffinches, two or three in dogs, two in rabbits, six in cattle and one in goats.
There are bound to be more - it's a question of how much effort has been put into looking for them, according to Dr John Doorbar, of the Virology Division of the Medical Research Council's National Institute for Medical Research, Mill Hill, London.
Since papillomaviruses are found in mammals, birds and reptiles, but not in amphibians or fish, one could infer that they were probably present in ancestors of the former group, the "amniotes" such as the dinosaurs, which emerged some 360 to 286 million years ago, according to a study by Ruth Tachezy at the Institute of Haematology in Prague, with Prof Marc Van Ranst in Belgium and colleagues in America. "This means that species-specific papillomaviruses could potentially infect more than 20,000 living species, living in virtually every habitat of the planet," they concluded. "The papillomaviruses could be the oldest, largest, and most diverse viral family on the planet."
There are an estimated 500,000 new cases of cervical cancer across the world, making it the second most frequent cancer in women, leading to around 270,000 deaths. However, two new vaccines, one developed by Merck and one by GlaxoSmithKline, can successful target the cancer-causing types of HPV. Over the coming decades, a few branches of this vast family tree of viruses may well go extinct.
GGG Ping.
BUSH did it.
Ex-squeeze me?
What's a couple of orders of magnitude between friends?
Wonder if Dr. Soranus knows the Ho in the article?
How come it never evolved into anything other than a virus?
/h
:'D
...papillomaviruses are found in mammals, birds and reptiles, but not in amphibians or fish...
Pretty well rules out handling frogs.
Every ten seconds a woman is catching a papilloma virus. She must be found and stopped.
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Medic alert!
Nonsense. Scientists can't even make up their minds if: salt, coffee, water, beer, fat, chocolate, sex, etc., etc.: is good for you. But they can figure out what is the oldest virus and how it evolved?
And yet we still have these liberal wackos telling our kids in school that just put on a condom and you'll be protected. I would have thought that a lawsuit would've occurred by now, as this would be such an easy case to win. Kids aren't told that you can get this on your thighs, butt, face, and any place else that comes in contact with an infected area (by female mucus), yet it's the most prevalent of all STD's.
The oldest human virus.
The next bird flu is just around the corner.
Ex-squeeze me?
One would have thought "Soranus" would have been a proctologist...
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