Nature.com

It’s time for animals – including humans – to admit that the bacteria, viruses and other microbes have won. Our bodies are home to many times more bacterial cells than animal cells and countless trillions of viruses. Ancient retroviruses make up a good size chunk of our genome. Now, scientists have discovered that most any virus can set up shop in an animal’s genomes and lay dormant for millions of years.

A scan of 44 mammal genomes, plus those of several mosquito and tick vectors and two birds that could serve as reservoirs, has uncovered DNA sequences that can be traced to 10 different families of viruses, including some related to viruses that cause hepatitis B, Ebola, rabies and dengue. Most of the viral sequences are riddled with enough mutations to be considered junk, but some appear to encoding working genes co-opted by their host. The work is published online today in the journal PLoS Genetics.

It’s not obvious how all these viruses got into animal genomes. The researchers, Aris Katzourakis at the University of Oxford, UK, and Robert Gifford at Rockefeller University in New York, searched specifically for viruses that aren’t retroviruses, which are obligated to copy their DNA into hosts. Many but not all of the viruses infect their hosts persistently or replicate inside of the nucleus, however, offering ample opportunity to take up residence in the genomes of germ cells.

The work is just a first look at all the non-retroviruses in the animal genome, but Katzourakis and Gifford turned up a few interesting findings. For instance, their scan identified sequences from filoviruses, the family Ebola belongs to, in the genomes of bats, tarsiers, several rodents, opossums and even wallabies. This hints that filoviruses have a much wider host range than the primate and bat species which these viruses are known to infect.

The paper also hints at unknown ancient transmissions of viruses between hosts. The bottlenose dolphin genome, it turns out, is home to sequences of a kind of parvovirus similar to one found in birds, suggesting that the viruses may have jumped between mammals and birds in the past.

Most of these sequences are junk, so filled with mutations that they can’t make working proteins. But some of the viral sequences might do something inside their hosts. One example is a bornavirus gene called EBLN-1 that took up residence in ancient primate genomes some 50 million years ago and survives intact in many modern primates, including humans. A similar protein latches onto RNA in bornaviruses, so it might do the same in primates as part of a viral defence mechanism, Gifford speculates.

Like the ancient retroviruses locked inside animal genomes, these viruses offer a window into infections that occurred millions of years ago.

“People who are looking at the ecology of those diseases, they very much work in recent time and they have no assumptions that it’s an old system that might have evolved over billions of years,” says Gifford. “The data that we’re finding is really contradicting that and providing the first evidence that these are really old relationships between hosts and viruses, and I think it’s really critical to how we underestand them to get that context right.”

 

Comments

This is a key paper with major implications. Hundreds of viruses appear to have infiltrated the human genome. The important consequence of this is that the proteins
of today’s viruses resemble our own. Numerous BLASTs of translated viral DNA vs.the human proteome are shown at this site named Pandora’s
box for obvious reasons. Small contigous amino acid stretches of 5 or more amino acids within human proteins exactly match those in the current virome (Vatches = viral matches).
Upon infection these viral proteins are likely to seed havoc within the host’s protein networks, acting as dummy ligands, decoy receptors or by interactome interference. This has major implications for understanding how viruses contribute to disease and several examples are shown.For example it
would appear that such viral insertions,repeated over evolutionary time, are
responsible for the creation of gene families. HSV-1 and HSV-2 are homologous to many kinases,
and the cytomegalovirus to many chemokine receptors.

The viruses implicated as risk factors in Alzheimer’s disease, schizophrenia and Parkinson’s disease all express proteins that are homologous to hundreds
of susceptibity gene products in these diseases.This suggests that genes and risk factors act together, and that each may be a risk factor precisely because of such matches. In addition, given such homology at both the DNA and protein level, it is likely that some gene association studies, using blood samples, have been
indexing infection as well as identifying key susceptibility genes.

Excerpt:

Now, researchers from the University of Texas Medical Branch at Galveston, UCLA, Harvard University, the U.S. Army Medical Research Institute of Infectious Diseases and Cornell University have teamed up to develop and test a broad-spectrum antiviral compound capable of stopping a wide range of highly dangerous viruses, including Ebola, HIV, hepatitis C virus, West Nile virus, Rift Valley fever virus and yellow fever virus, among others.

But not to worry, according to officials. The vials were old and lost long before new documentation procedures were put in place. Besides, the lab is being expanded and updated with the latest security devices. Such reassuring mantras resound after every oil and chemical spill, radioactive discharge from nuclear power plant (more frequent than generally realized), black-market uranium sale, and mishandled nuclear bomb: “It may seem dangerous, but trust us – there wasn’t enough poison to hurt a fly and besides, we’re sure we recovered everything.”

Very likely – hopefully – at Fort Detrick they did. But the most important question remains unanswered: can any BSL-4, the labs with the deadliest, often highly contagious, bacteria and viruses, ever be truly fail-safe? After all, at some point that old storeroom in Fort Detrick was state-of-the-art. Human error applies not only to daily procedures, but to equipment that always seems so pristine when new. Proponents of BSL-4s argue that without these research labs we stand defenseless against a natural outbreak of disease or bio-terrorist attack. And, they say, the labs are so safe that the chances of a disease-spreading breach approach zero.

The problem is, neither of these assertions is strictly true. Vaccines against Level-4 Ebola and Marburg viruses have been developed in Level-2 labs by inserting their DNA into non-pathogenic viruses that can trigger immune responses just as definitively as the deadly pathogen. Scientists can therefore develop vaccines against deadly bacteria and viruses without actually handling the germs themselves. And the Level-4 labs may very well make our world more dangerous rather than safer and more secure. However modern and up-to-date a laboratory, it is still subject to human error, violence, neglect, and systemic breakdown. The Foot and Mouth Disease (FMD) outbreak in Great Britain in 2007 was due, according to the British government’s inquiry, to “poor training and incompetence” and a “creeping degradation of standards”, while the 2001 outbreak was attributed by the government to an employee who smuggled out a vial of FMD from his lab.

“Creeping degradation” is probably responsible for most industrial and infrastructural accidents. The case of Plum Island off the northeast coast of Long Island, New York, home to a now-closed Level-4 lab, illustrates the problem. Many believe Plum Island responsible for Lyme Disease, borne by deer swimming five miles from the island to the Connecticut coast near Lyme where the first outbreaks occurred. Lab 257 by Michael Carroll details how protocols and procedures at Plum Island eventually unraveled. Countless small oversights and flaws in equipment, procedures, and human judgment tend to build up over time to generate distinct vulnerabilities until an otherwise controllable opportunistic event spins out of control.

It is often claimed that BSL-4s have a flawless safety record, although the 9,220 recovered vials seem to undermine that claim. More importantly, only two Level-4 labs have operated in the United States until recently and their documentation has been in disarray, as Fort Detrick’s spokesperson admitted to explain how the vials went missing.

There is, in fact, no real documentation that BSL-4 labs have been operating safely. As with the oft-ignored low-level radioactive releases from nuclear power plants, small accidents can be ignored or covered up; it takes a major disaster to enter public consciousness. Recently, the city of Boston had to admit that the news of the infection of three BSL-2 lab workers in a lab had been suppressed by the lab and city officials. Mayor Menino assured us that if the public had been in danger, they would have told us sooner. Granted, Level-2 labs are not built to be foolproof and the diseases harbored there are far milder than in BSL-4s, but when infection at a BSL-2 is kept under wraps, would a more serious threat have been publicized, especially with no real emergency response mechanism in place in most communities?

According to the Sunshine Project, “Three Texas A&M University biodefense researchers were infected with the biological weapons agent Q Fever in 2006. The infections were confirmed in April of that year, but Texas A&M officials did not report them to the Centers for Disease Control (CDC), as required by law. Instead, Texas A&M officials covered the infections up until now, illegally failing to disclose them despite freedom of information requests dating back to October 2006.” This was in addition to a brucella infection at the lab, news of which was also withheld from the public. In response to these events, the Center for Disease Control ordered the lab to shut down its bioweapons research, citing – in a detailed report issued August 31, 2007 – a host of violations of basic safety protocols at the lab. Other accidents at BSL-3s have recently occurred at the University of New Mexico (anthrax, 2003 and unidentified pathogen in 2004); Medical University of Ohio (2004, Level-3 Valley Fever); University of Chicago (2005, Level 3, possibly anthrax or plague); and UC Berkeley (2005, Level 3 aerosolized, weaponized Rocky Mountain Spotted Fever). From 2005-2006, University of Wisconsin at Madison (UW) researchers made and manipulated copies of the Ebola virus genome even though the federal government stipulates that such research must take place at a BSL-4. (It should be noted that Level-3 pathogens can be every bit as dangerous as Level 4s and include many of the more contagious germs; it’s just they’ve been shown to respond to antibiotics). All these cases occurred after 2001, when the through-the-mail anthrax attacks supposedly led to tighter security and more sophisticated protocols at BSL-3s and BSL-4s.

The dangers posed by biolabs often fly under the radar, but that may be changing. The General Accounting Office, in a report released this past September 21st, stated that the rapid – and often unregulated – proliferation of Level 3 and Level 4 labs places the public at significant risk. The public would do well to question the knee-jerk “security at all costs” policy of the federal government which threatens to build up stores of the world’s deadliest organisms across the United States. As for proponents’ arguments that the labs are absolutely safe and absolutely necessary, we shall address them soon in another post.

http://www.huffingtonpost.com/barton-kunstler-phd/biolabs-multiplying-like_b_358985.html