Back in January I blogged about how the physical constraint of capsid size may be forcing some viruses to squeeze their genomes into such a compact state that their genes overlap. Now we visit the other end of the scale to the largest virus yet discovered, appropriately called Megavirus chilensis, found in ocean waters off the coast of Chile.
As one of the paper's coauthors told BBC News, "You don't need an electron microscope to see it; you can see it with an ordinary light microscope." Each virus particle is about 680 nm across, or just under a micrometer, making it just barely visible as specks by light microscopy. They're structurally interesting, bearing a covering of fibers ("hair") all over the surface, and a five-pronged star-shaped structure on one vertex that the authors have called a "stargate", which the virus uses to release its nuclear material into the host cytoplasm.
Showing posts with label virus. Show all posts
Showing posts with label virus. Show all posts
Sunday, October 16, 2011
Sunday, January 09, 2011
House Too Small? – Overlapping Genes in Viruses
Protein coding genes are complicated things: the four bases of DNA are arranged into triplet codons, each of which codes for one of 21 (more or less) amino acids, which are strung up in a polypeptide chain, folded into a complex 3-dimensional structure where precise shape and chemistry determines function... It would seem that any perturbation would throw this finely-tuned system off-kilter.
Even more outrageous is the notion that genes can overlap and still code for perfectly functional proteins, because this implies that, for part of the gene at least, a different reading frame still has functional meaning. This flies against our intuition that frame-shift mutations are the deadliest of all, and has been likened to taking a paragraph of text, moving all the spaces between words down by a character, and still being able to read it, but this time with a completely different meaning!
Viruses, though, are capable of this sort of contortion, and a number of hypotheses have been proposed to explain why they find it necessary to do so. Is it a way to reduce the overall genome length in the face of a high mutation rate? Or is it a means to couple together the expression of more than one gene? Looking at a number of viral genomes, a team from Italy and the UK claim to have found the reason: overlapping genes are a response to the constraints placed by viral capsid size.
For viruses that use RNA for their genetic material, there is a known inverse relationship between genome size and gene overlap: the longer the genome, the less gene overlap is present. They confirmed that this also held for DNA viruses. But when they grouped viruses by the kind of capsids they have–icosahedral vs. flexible–they found that this relationship is strong in the icosahedral capsid viruses, but weak in those with flexible capsids. Capsids are protein 'coats' that encase the viral genome; icosahedral capsids are particularly rigid and constrained in size, because their geometric configuration (icosahedra are one of the five Platonic solids of classical geometry) is the result of the interlocking of the protein units that make up the coat. There are precise mathematical rules that govern the assembly of these units.
On the surface, it seems like an extreme solution, even reminiscent of the infamous Bed of Procrustes. These viruses appear to have found a way of surviving the ordeal. It's so striking because we wouldn't expect to see what is patently a physical constraint leaving such a distinctive genomic signature, the latter being strictly informational. At the molecular level, though, there may be a fuzzier line between the two.
This is one of those things which writers used to attribute to the 'ingenuity of Nature', but speaking in materialist terms:
Even more outrageous is the notion that genes can overlap and still code for perfectly functional proteins, because this implies that, for part of the gene at least, a different reading frame still has functional meaning. This flies against our intuition that frame-shift mutations are the deadliest of all, and has been likened to taking a paragraph of text, moving all the spaces between words down by a character, and still being able to read it, but this time with a completely different meaning!
Viruses, though, are capable of this sort of contortion, and a number of hypotheses have been proposed to explain why they find it necessary to do so. Is it a way to reduce the overall genome length in the face of a high mutation rate? Or is it a means to couple together the expression of more than one gene? Looking at a number of viral genomes, a team from Italy and the UK claim to have found the reason: overlapping genes are a response to the constraints placed by viral capsid size.
For viruses that use RNA for their genetic material, there is a known inverse relationship between genome size and gene overlap: the longer the genome, the less gene overlap is present. They confirmed that this also held for DNA viruses. But when they grouped viruses by the kind of capsids they have–icosahedral vs. flexible–they found that this relationship is strong in the icosahedral capsid viruses, but weak in those with flexible capsids. Capsids are protein 'coats' that encase the viral genome; icosahedral capsids are particularly rigid and constrained in size, because their geometric configuration (icosahedra are one of the five Platonic solids of classical geometry) is the result of the interlocking of the protein units that make up the coat. There are precise mathematical rules that govern the assembly of these units.
 |
| Icosahedral adenoviruses (electron micrographs) with cartoon of icosahedron. (Wikimedia Commons) |
On the surface, it seems like an extreme solution, even reminiscent of the infamous Bed of Procrustes. These viruses appear to have found a way of surviving the ordeal. It's so striking because we wouldn't expect to see what is patently a physical constraint leaving such a distinctive genomic signature, the latter being strictly informational. At the molecular level, though, there may be a fuzzier line between the two.
This is one of those things which writers used to attribute to the 'ingenuity of Nature', but speaking in materialist terms:
"In effect, the capsid poses an engineering problem for the creation of genomic novelty, and gene overlap is the way around it."
Friday, November 19, 2010
Stowaway Viruses
Most of us tend not to think too much about viruses until we (or our computers...) get one, and then we start to wonder what medical science is up to if after all this time we still don't have a cure for viral disease.
What we don't realize is that lurking in our genomes, and indeed the genomes of most animals, are viral stowaways. Biologists are no strangers to stowaways - the mitochondrion is one of the best examples, once a free-living bacterium now captured to be the energy generators of the eukaryotic cell. But at least one can see a mitochondrion. Stowaway viruses, more properly called endogenous viral elements (EVEs), have worked their way right into the stuff of life itself, inserting the instructions for making more of themselves into our DNA.
For one group of viruses, the retroviruses, this does not come as a surprise. Retroviruses invade the cell carrying their genomes on RNA, and then use the enzyme reverse transcriptase (hence their name) to write their genome into DNA which is then inserted into the host genome. From this seat in the host genome, their genes are activated and set in motion the machinery for producing and assembling new virus particles. They can also lie quiescent for generations, piggybacking along the divisions of their (increasingly numerous) hosts. It's been known for a long time that much of the human genome is made up of former EVEs that have mutated and are no longer functional, becoming part of the 'junk DNA' that litters our genomes.
A recent intensive search of animal genome sequences, however, has found that non-retroviruses can form EVEs too. This is part of a clutch of recent studies on the diversity and evolution of EVEs, that seems to also pose a philosophical question - what does it really mean to be human? The human cells in our bodies are already outnumbered by the bacteria that live in our gut, on our skin, under our nails, and virtually every other surface on us. And now we find that our genomes don't really belong to us either?
EVEs in the genome sequence are being used as a 'fossil record' of viral infection events in our human past, being of value in reconstructing the history of virus and human evolution. Yet these ancient events still have very immediate consequences for us today. Schizophrenia is a widespread and serious mental disorder that is extremely debilitating to its sufferers. It has long been treated as a purely psychiatric disorder, with the exact physiological basis remaining obscure. Yet some puzzling observations about the disease remained:
This observation has been used to support the hypothesis that schizophrenia is caused by an EVE called HERV-W, which has also been implicated in the onset of multiple sclerosis. Although the endovirus theory of schizophrenia is still far from being textbook truth (the theory's main supporter, Fuller Torrey, has weathered considerable controversy), it is certainly thought-provoking, and will certainly draw more attention to the burgeoning field of animal endoviruses.
What we don't realize is that lurking in our genomes, and indeed the genomes of most animals, are viral stowaways. Biologists are no strangers to stowaways - the mitochondrion is one of the best examples, once a free-living bacterium now captured to be the energy generators of the eukaryotic cell. But at least one can see a mitochondrion. Stowaway viruses, more properly called endogenous viral elements (EVEs), have worked their way right into the stuff of life itself, inserting the instructions for making more of themselves into our DNA.
For one group of viruses, the retroviruses, this does not come as a surprise. Retroviruses invade the cell carrying their genomes on RNA, and then use the enzyme reverse transcriptase (hence their name) to write their genome into DNA which is then inserted into the host genome. From this seat in the host genome, their genes are activated and set in motion the machinery for producing and assembling new virus particles. They can also lie quiescent for generations, piggybacking along the divisions of their (increasingly numerous) hosts. It's been known for a long time that much of the human genome is made up of former EVEs that have mutated and are no longer functional, becoming part of the 'junk DNA' that litters our genomes.
A recent intensive search of animal genome sequences, however, has found that non-retroviruses can form EVEs too. This is part of a clutch of recent studies on the diversity and evolution of EVEs, that seems to also pose a philosophical question - what does it really mean to be human? The human cells in our bodies are already outnumbered by the bacteria that live in our gut, on our skin, under our nails, and virtually every other surface on us. And now we find that our genomes don't really belong to us either?
EVEs in the genome sequence are being used as a 'fossil record' of viral infection events in our human past, being of value in reconstructing the history of virus and human evolution. Yet these ancient events still have very immediate consequences for us today. Schizophrenia is a widespread and serious mental disorder that is extremely debilitating to its sufferers. It has long been treated as a purely psychiatric disorder, with the exact physiological basis remaining obscure. Yet some puzzling observations about the disease remained:
Schizophrenia is usually diagnosed between the ages of 15 and 25, but the person who becomes schizophrenic is sometimes recalled to have been different as a child or a toddler—more forgetful or shy or clumsy. Studies of family videos confirm this. Even more puzzling is the so-called birth-month effect: People born in winter or early spring are more likely than others to become schizophrenic later in life. It is a small increase, just 5 to 8 percent, but it is remarkably consistent, showing up in 250 studies. That same pattern is seen in people with bipolar disorder or multiple sclerosis.
This observation has been used to support the hypothesis that schizophrenia is caused by an EVE called HERV-W, which has also been implicated in the onset of multiple sclerosis. Although the endovirus theory of schizophrenia is still far from being textbook truth (the theory's main supporter, Fuller Torrey, has weathered considerable controversy), it is certainly thought-provoking, and will certainly draw more attention to the burgeoning field of animal endoviruses.
Thursday, April 30, 2009
Communicating the Swine influenza A (H1N1) crisis
Informed or misinformed?
With the emergence of Swine influenza A (H1N1), a phenomenal amount of news is available via the internet. There are numerous webpages, blogs (and their rss feeds), facebook walls, notes and pages and these days, tweets as well.
The chatter is welcome instead of silence, but with any communication medium, the undiscerning reader runs the chance of being misinformed almost as easily. This ability of people to be misinformed and pass on incorrect news was discussed last week regarding Twitter. Agencies are doing their best to fight back. e.g. CDC Emergency's latest tweet when I was writing this said, "CDC reminds you that you can NOT get swine flu from eating pork...." and follows with a link to their FAQ.
New sites I refer to include:
Too much information - a summary?
Teachers like Cheng Puay who are primary communicators, are using such information to educate and prepare students. They are certainly armed with more effective tools these days!
With the emergence of Swine influenza A (H1N1), a phenomenal amount of news is available via the internet. There are numerous webpages, blogs (and their rss feeds), facebook walls, notes and pages and these days, tweets as well.
The chatter is welcome instead of silence, but with any communication medium, the undiscerning reader runs the chance of being misinformed almost as easily. This ability of people to be misinformed and pass on incorrect news was discussed last week regarding Twitter. Agencies are doing their best to fight back. e.g. CDC Emergency's latest tweet when I was writing this said, "CDC reminds you that you can NOT get swine flu from eating pork...." and follows with a link to their FAQ.
The chance of being misinformed increases when a reader engages in multi-tasking activities or lays claim to "reading" hundreds of sources - in a crisis I am reluctant to rely on rss-skimming friends for specific facts, but rather, use their pointers as potential sources of information pending investigation before further forwards. And beware that one time you relax your guard - it will be the occasion in which you contribute to the problem of misinformation!
Be a source of reliable information
Avid web-readers can be a resource to friends and family in such trying times by being a source of reliable and updated information. In addition to television news from international and local news sites, I find reading just a few reliable sources on the net thoroughly and reviewing the information for specific lessons helpful - I find it useful in responding with practical applications including communication and myth-busting in daily conversation!
During the SARS outbreak in 2003, I found the face to face conversations with like-minded friends (they happen to helpfully also be biology grads) to be extremely helpful. These conversations were supplemented by email discussions, and all of it helped me in decision making and preparations for a large meeting of about 300 people at the university (Biodiversity of Singapore Symposium). This pattern was employed during the 2004 Indian Ocean Tsunami - the information completely transformed my approach about how to help.
The need to communicate
Will large, global agencies tell it like it is? I was quite surprised by the aggressive updates of the the World Health Organisation (WHO) during the SARS outbreak - I felt information was served up as soon as it was acquired, and this was later expressed as a critical strategy in the WHO Outbreak Communcation Guidelines [pdf], which advocate "Trust, Early warning, Transparency, An understanding of the public, suggesting mitigation measures and an aggressive Communications plan."
For the H1N1, I find these same (as in SARS) international and local sources useful:
- WHO Disease Outbreak News
- Center for Disease Control and Prevention: Swine Influenza (Flu): cdc.gov/swineflu/
- CDC has a twitter account, @CDCemergency! Hat tip - Kevin
- Ministry of Health, Singapore: Update on Global Human Swine Influenza - helpfully this URL: moh.gov.sg, brings you right there.
New sites I refer to include:
- Channel News Asia special on the Swine Flu Outbreak - note the useful, simple URL: channelnewsasia.com/swineflu/
- CNN Health: Swine Flu
- BBC: Swine Flu Special Report
- News aggregators (search term = "swine flu"): Google and Yahoo
Besides the very helpful graphics and background pieces, archive stories and supplemental news on social, economic and other aspects, the mainstream media is important for its opinion pieces, especially by experienced medical journalists. And alternative views of seasoned writers help keep a perspective at times, e.g. see Simon Jenkins' "Swine flu? A panic stoked in order to posture and spend." The Guardian, 29 April 2009.
Singapore - see the Ministry of Health's webpage
In Singapore, where the WHO Outbreak Communcation Guidelines meeting was held, the reliable source of updated information about status and core health issues is available at the Ministry of Health. The "Highlights page" now carries the "Update on Global Human Swine Influenza" - there is text and video of the minister's media update which is useful. The site could profit from a dedicated section, a useful rss feeds for this developing situation and perhaps, twitter as nudged by @acroamatic.
Too much information - a summary?
All this reliable information poses another problem - it is A LOT of information. A summary would be helpful but run the risk of sacrificing accuracy. Also with news updates and changes almost every day during such incidents, these would need to be regularly updated.
Well information dissemination is critical to limiting the further spread of infections and a "lack of information and knowledge about a global outbreak ... makes all affected people vulnerable, especially health professionals who need accurate and up-to-date information to care for patients and undertake crucial research."
However "... health information can [now] be rapidly accumulated and disseminated through the internet to the global medical community. .. Just-in-time (JIT) lectures, which target educators, can help to improve the dissemination of information in a health crisis." (Chotania, R. A., R. E. LaPorte, F. Linkov, S. Dodanic, D. Ahmed & K. M Ibrahim, 2003. Just-in-time lectures: SARS. The Lancet, 361 (9373): 1996. [7 June 2003: doi:10.1016/S0140-6736(03)13586-6])
Their paper recounts this approach during SARS which apparently borrowed a term from a manufacturing concept: just-in-time lectures (JIT) - these were rapidly assembled presentations that informed users could adopt, incorporated the brevity of a slideshow, distributed rapidly electronically, updated frequently and from what I see properly labelled to reflect the specific version.
The Just-in-time Swine influenza lecture
As a result, here it is: "Just-in-Time Lecture: Swine influenza A (H1N1) Outbreak in US & Mexico: Potential for a Pandemic," by Rashid A. Chotani. Uniformed Services University of the Health Sciences (USUHS). Updated daily. The html and powerpoint versions are available at the Supercourse site at the WHO Collaborating Center, University of Pittsburgh.
Pointing to the latest update
In response to an email query, he said, "Please use, post and circulate as widely as possible. .. I update the presentation everyday (some time twice)."
In light of his statement and the awareness of the potential of rapidly changing information, I abandoned any thought of using a slideshare embed of Version 3 (28 Apr 2009), but simply point back directly to the Supercourse site, for the reader to obtain the most updated version.
The slideshow is simple and clear for clinicians and biology teachers to use directly for briefings. The explanation of terms that are broached before diving in further is critical in clarifying the use of specific terms and the different sections are clearly spelled out.
Likewise in Singapore, despite the web2.0 shortcomings, the MOH webpage page includes a pdf slideshow which teachers and organisation communication teams will find useful for briefing or disseminating to students and staff. THe MOH slideshow reviews details of the local status with a breakdown of cases and types and sort of control measures that are being adopted and enforced.
Teachers like Cheng Puay who are primary communicators, are using such information to educate and prepare students. They are certainly armed with more effective tools these days!
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