This is quite possibly the best video ever made showing exactly how the flu virus gets into your body and makes a gajillion copies of itself at your expense. You thought the movie theatre scene in "Outbreak" was bad? This is three minutes and thirty-nine seconds of pure infectious delight.
Recommended viewing times: while healthy, not in a crowded place, and *before* lunch.
How A Virus Invades Your Body (NPR)
© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation
Showing posts with label influenza. Show all posts
Showing posts with label influenza. Show all posts
Monday, October 26, 2009
Tuesday, September 15, 2009
Old Flu Drug, New Hope
A QUANTUM OF SCIENCE
When vaccines fail, antiviral drugs might make the difference between life and death
The seasonal flu vaccine is already being administered and a special vaccine targeting H1N1 will soon follow, but for some people a vaccine may not be enough. Children, the elderly and immunocompromised individuals are at high risk for complications from influenza. For those already infected a vaccine does no good, but fortunately, antiviral medications are available when the flu turns life-threatening.
The most well-known anti-influenza drug is TamiFlu (its official name is Oseltamivir). TamiFlu is taken orally, usually for a five-day course of treatment. Approved in 1999, it has been used to treat 50 million people to date. Currently, TamiFlu is usually reserved for serious, potentially life-threatening cases in an attempt to prevent the flu virus from mutating into a form resistant to the drug. Indeed, five cases of TamiFlu-resistant H1N1 have already been reported but overall the rate of resistance flu cases remains low (around 1.2%).
Recently, a drug called Peramivir has been developed and is on the fast track to approval by the FDA. This is not a new drug – it was abandoned in 2001 by Johnson and Johnson due to low oral availability – but in 2005 concerns over Avian flu caused drug-makers to reexamine the compound and begin testing it as an intravenous medication. Recent studies show a single intravenous dose of Peramivir is as effective as the full five-day course of oral treatment with TamiFlu. Additionally, adverse drug reactions were less common with Peramivir.
Both TamiFlu and Peramivir act by inhibiting the same viral enzyme, neuraminidase. This enzyme allows viral particles to escape infected cells and go out in the bloodstream where they can find new cells to infect. When TamiFlu or Peramivir inhibit the viral neuraminidase, viral particles remain trapped inside infected cells until the body’s immune system can respond, usually with macrophages (literally "big eaters") that engulf the infected cell and digest it, destroying the viral particles along with the cell.
Additional advantages of Peramivir include its single-dose effectiveness. There have been reports of individuals hoarding TamiFlu pills and threatening the supply of the drug, but that cannot happen with a drug which can only be administered intravenously.
For more information:
Study: New Drug Fights Flu as Well as TamiFlu
TamiFlu (Wikipedia article)
TamiFlu-resistant H1N1 cases reported
© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation
When vaccines fail, antiviral drugs might make the difference between life and death
The seasonal flu vaccine is already being administered and a special vaccine targeting H1N1 will soon follow, but for some people a vaccine may not be enough. Children, the elderly and immunocompromised individuals are at high risk for complications from influenza. For those already infected a vaccine does no good, but fortunately, antiviral medications are available when the flu turns life-threatening.
The most well-known anti-influenza drug is TamiFlu (its official name is Oseltamivir). TamiFlu is taken orally, usually for a five-day course of treatment. Approved in 1999, it has been used to treat 50 million people to date. Currently, TamiFlu is usually reserved for serious, potentially life-threatening cases in an attempt to prevent the flu virus from mutating into a form resistant to the drug. Indeed, five cases of TamiFlu-resistant H1N1 have already been reported but overall the rate of resistance flu cases remains low (around 1.2%).
Recently, a drug called Peramivir has been developed and is on the fast track to approval by the FDA. This is not a new drug – it was abandoned in 2001 by Johnson and Johnson due to low oral availability – but in 2005 concerns over Avian flu caused drug-makers to reexamine the compound and begin testing it as an intravenous medication. Recent studies show a single intravenous dose of Peramivir is as effective as the full five-day course of oral treatment with TamiFlu. Additionally, adverse drug reactions were less common with Peramivir.
Both TamiFlu and Peramivir act by inhibiting the same viral enzyme, neuraminidase. This enzyme allows viral particles to escape infected cells and go out in the bloodstream where they can find new cells to infect. When TamiFlu or Peramivir inhibit the viral neuraminidase, viral particles remain trapped inside infected cells until the body’s immune system can respond, usually with macrophages (literally "big eaters") that engulf the infected cell and digest it, destroying the viral particles along with the cell.
Additional advantages of Peramivir include its single-dose effectiveness. There have been reports of individuals hoarding TamiFlu pills and threatening the supply of the drug, but that cannot happen with a drug which can only be administered intravenously.
For more information:
Study: New Drug Fights Flu as Well as TamiFlu
TamiFlu (Wikipedia article)
TamiFlu-resistant H1N1 cases reported
© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation
Thursday, May 21, 2009
A single amino acid
A QUANTUM OF SCIENCE
Why does the more lethal H5N1 Avian flu not infect humans more readily?
Several references have been made now to the "nightmare scenario" in which genes from the more lethal Avian flu (H5N1) reassort with the less dangerous but more infective Swine flu (H1N1), generating a hybrid that is both lethal and infective. We have yet to talk much about why the H5N1 strain is harder for people to catch – so hard that in some years there are only a single-digit number of cases.
Certainly, the lethality of H5N1 inhibits its spread. In epidemiological terms, the virus kills faster than it spreads, leading to a reproduction number at or below one. In a recent paper, researchers show that a single amino acid change in the sequence of the viral polymerase gene (PB2) results in a dramatic difference in both temperature tolerance and infectivity.
Scientists at University of North Carolina at Chapel Hill found that the H5N1 virus required the higher temperatures found in its bird hosts (around 40 degrees Celsius) in order to be highly infective. At 32 degrees Celsius - the temperature of the cells found in human nasal passages called HAE, or human airway epithelium – the H5N1 virus became sticky and did not effectively infect those cells. The reason for this? A single amino acid at position 627 of the polymerase protein of the H5N1 virus was changed, allowing it to be glycosylated - chemically modified to bear a particular sugar residue. Researchers were able to prove this by genetically altering a human influenza virus (which infected cells optimally at 32 degrees Celsius) at position 627, changing just that one amino acid to one that could be glycosylated. The resulting human virus was not capable of creating an infection in human airway epithelial cells, demonstrating an attenuation of the formerly infective human influenza virus. Further modification of viral coat proteins fully attained an "avian" level of temperature sensitivity.
This research is important because it significantly adds to our understanding of the molecular process by which the influenza virus mounts a successful infection in either of its principal hosts (birds or humans). Scientists who sequence previously unknown strains of influenza isolated from patients can now rapidly assess the polymerase gene (PB2) and determine quickly whether it is an avian strain or one more evolved for humans. Not only the treatments recommended but also the course of a widespread epidemiological event could be affected by this. Further, scientists searching for the molecular keys to understanding the mutations of various influenza strains can now look more effectively for such alterations, granting insight into the process of interspecies spread of the virus.
Perhaps most importantly, these findings help to partially allay fears that H5N1 is likely to reassort with H1N1 – since avian flu infects HAE cells poorly due to their intolerance for colder temperatures, we are less likely to endure that kind of hybrid virus.
For more information:
Avian Influenza Virus Glycoproteins Restrict Virus Replication and Spread through Human Airway Epithelium at Temperatures of the Proximal Airways.
© A Quantum of Science / Peter Smalley (2009)
Reproduction with attribution is appreciation
Why does the more lethal H5N1 Avian flu not infect humans more readily?
Several references have been made now to the "nightmare scenario" in which genes from the more lethal Avian flu (H5N1) reassort with the less dangerous but more infective Swine flu (H1N1), generating a hybrid that is both lethal and infective. We have yet to talk much about why the H5N1 strain is harder for people to catch – so hard that in some years there are only a single-digit number of cases.
Certainly, the lethality of H5N1 inhibits its spread. In epidemiological terms, the virus kills faster than it spreads, leading to a reproduction number at or below one. In a recent paper, researchers show that a single amino acid change in the sequence of the viral polymerase gene (PB2) results in a dramatic difference in both temperature tolerance and infectivity.
Scientists at University of North Carolina at Chapel Hill found that the H5N1 virus required the higher temperatures found in its bird hosts (around 40 degrees Celsius) in order to be highly infective. At 32 degrees Celsius - the temperature of the cells found in human nasal passages called HAE, or human airway epithelium – the H5N1 virus became sticky and did not effectively infect those cells. The reason for this? A single amino acid at position 627 of the polymerase protein of the H5N1 virus was changed, allowing it to be glycosylated - chemically modified to bear a particular sugar residue. Researchers were able to prove this by genetically altering a human influenza virus (which infected cells optimally at 32 degrees Celsius) at position 627, changing just that one amino acid to one that could be glycosylated. The resulting human virus was not capable of creating an infection in human airway epithelial cells, demonstrating an attenuation of the formerly infective human influenza virus. Further modification of viral coat proteins fully attained an "avian" level of temperature sensitivity.
This research is important because it significantly adds to our understanding of the molecular process by which the influenza virus mounts a successful infection in either of its principal hosts (birds or humans). Scientists who sequence previously unknown strains of influenza isolated from patients can now rapidly assess the polymerase gene (PB2) and determine quickly whether it is an avian strain or one more evolved for humans. Not only the treatments recommended but also the course of a widespread epidemiological event could be affected by this. Further, scientists searching for the molecular keys to understanding the mutations of various influenza strains can now look more effectively for such alterations, granting insight into the process of interspecies spread of the virus.
Perhaps most importantly, these findings help to partially allay fears that H5N1 is likely to reassort with H1N1 – since avian flu infects HAE cells poorly due to their intolerance for colder temperatures, we are less likely to endure that kind of hybrid virus.
For more information:
Avian Influenza Virus Glycoproteins Restrict Virus Replication and Spread through Human Airway Epithelium at Temperatures of the Proximal Airways.
© A Quantum of Science / Peter Smalley (2009)
Reproduction with attribution is appreciation
Wednesday, May 20, 2009
Mapping H1N1
A QUANTUM OF SCIENCE
Where in the world is H1N1?
The spread of H1N1 around the world has significant implications for the etiology and epidemiology of the disease, as well as the global health infrastructure’s response to it. Raw numbers alone do not tell the story as well as this single image, taken from the WHO pandemic alert and response website.
This map is current: as of today there are a global total of 10,243 laboratory-confirmed cases of H1N1 influenza that have been reported to the WHO, including 80 deaths (making the global mortality rate one death out of every 128 cases). While the actual number of total cases is inevitably somewhat higher due to the lagging nature of lab confirmations and reporting, what is more interesting is the distribution of the cases – and deaths – and what this might tell us about the past and future of H1N1.
Originally dubbed as Swine Flu, the official name for this strain of H1N1 is North American influenza, and indeed the overwhelming majority of the cases are in North America (93.8%). What is interesting to note is that 79 of the 80 confirmed deaths are also in North America (98.75%). Digging a little deeper into the distribution of deaths, we find that this is due to the large contribution of deaths from H1N1 in Mexico, where the mortality rate is one death for every 50.6 cases. That is two and a half times the global mortality rate, and eighteen times the mortality rate in the adjacent United States. With the sequencing of the H1N1 genome in Canada that was announced yesterday, no significant differences were found in strains isolated in Mexico versus those in the United States or Canada. While this is somewhat reassuring because it means there is not a more virulent strain on the loose in Mexico, it requires a different explanation. Some authorities have suggested Mexico has deficiencies in its health infrastructure, but others cite a cultural inhibition that may play a more pervasive role in preventing infected persons from seeking help until it is too late. In either case, however, countries with similar health infrastructures and cultures would be expected to have a similar mortality rate, and this has not yet been borne out (as the map’s number for Central and South America show).
Another point of interest brought out by the map of H1N1 cases to date are the non-North American hot spots. Japan is the leader of these, with 210 cases, followed almost evenly by Spain (107) and the United Kingdom (102). What is interesting about this is the far-flung locations of the hotspots outside North America. Nothing like the close distribution of cases in Mexico-US-Canada have been seen in these Asian and European hotspots. This could mean that there is something particular to North America that supports the infectivity of the viral strain; or it could mean that it is simply too soon, and the neighbors of these hotspots will soon show a commensurate rise in cases. It is worth noting that strains of influenza are known to show a strong geographical preference; the deadly Bird flu (H5N1) is almost unknown outside of the Far East, for reasons that scientists are still trying to elucidate. This also brings up the potential for reassortment of viral genes between H1N1 and H5N1, now that the former has entered the latter’s territory. Still, Japan has been aggressive about treating flu cases and currently Roche (the maker of Tamiflu) estimates that 35 million of the 50 million people who have been treated with Tamiflu are in Japan. It can be hoped that this aggressive treatment schedule will be effective in containing the possible hybridization of H1N1 with H5N1.
For more information:
WHO Epidemic and Pandemic Alert and Response
WHO H1N1 map (20-May-2009 version)
Tamiflu (Oseltamivir) information, including use in Japan
© A Quantum of Science / Peter Smalley (2009)
Reproduction with attribution is appreciation
Where in the world is H1N1?
The spread of H1N1 around the world has significant implications for the etiology and epidemiology of the disease, as well as the global health infrastructure’s response to it. Raw numbers alone do not tell the story as well as this single image, taken from the WHO pandemic alert and response website.
This map is current: as of today there are a global total of 10,243 laboratory-confirmed cases of H1N1 influenza that have been reported to the WHO, including 80 deaths (making the global mortality rate one death out of every 128 cases). While the actual number of total cases is inevitably somewhat higher due to the lagging nature of lab confirmations and reporting, what is more interesting is the distribution of the cases – and deaths – and what this might tell us about the past and future of H1N1.
Originally dubbed as Swine Flu, the official name for this strain of H1N1 is North American influenza, and indeed the overwhelming majority of the cases are in North America (93.8%). What is interesting to note is that 79 of the 80 confirmed deaths are also in North America (98.75%). Digging a little deeper into the distribution of deaths, we find that this is due to the large contribution of deaths from H1N1 in Mexico, where the mortality rate is one death for every 50.6 cases. That is two and a half times the global mortality rate, and eighteen times the mortality rate in the adjacent United States. With the sequencing of the H1N1 genome in Canada that was announced yesterday, no significant differences were found in strains isolated in Mexico versus those in the United States or Canada. While this is somewhat reassuring because it means there is not a more virulent strain on the loose in Mexico, it requires a different explanation. Some authorities have suggested Mexico has deficiencies in its health infrastructure, but others cite a cultural inhibition that may play a more pervasive role in preventing infected persons from seeking help until it is too late. In either case, however, countries with similar health infrastructures and cultures would be expected to have a similar mortality rate, and this has not yet been borne out (as the map’s number for Central and South America show).
Another point of interest brought out by the map of H1N1 cases to date are the non-North American hot spots. Japan is the leader of these, with 210 cases, followed almost evenly by Spain (107) and the United Kingdom (102). What is interesting about this is the far-flung locations of the hotspots outside North America. Nothing like the close distribution of cases in Mexico-US-Canada have been seen in these Asian and European hotspots. This could mean that there is something particular to North America that supports the infectivity of the viral strain; or it could mean that it is simply too soon, and the neighbors of these hotspots will soon show a commensurate rise in cases. It is worth noting that strains of influenza are known to show a strong geographical preference; the deadly Bird flu (H5N1) is almost unknown outside of the Far East, for reasons that scientists are still trying to elucidate. This also brings up the potential for reassortment of viral genes between H1N1 and H5N1, now that the former has entered the latter’s territory. Still, Japan has been aggressive about treating flu cases and currently Roche (the maker of Tamiflu) estimates that 35 million of the 50 million people who have been treated with Tamiflu are in Japan. It can be hoped that this aggressive treatment schedule will be effective in containing the possible hybridization of H1N1 with H5N1.
For more information:
WHO Epidemic and Pandemic Alert and Response
WHO H1N1 map (20-May-2009 version)
Tamiflu (Oseltamivir) information, including use in Japan
© A Quantum of Science / Peter Smalley (2009)
Reproduction with attribution is appreciation
Tuesday, May 19, 2009
Canadian scientists sequence H1N1 genome
A QUANTUM OF SCIENCE
Now we know the complete blueprint for H1N1; now what?
Today it was announced that scientists in Canada have fully sequenced the entire genome of the H1N1 influenza virus. While it's not the first viral genome to be fully sequenced, it is a landmark achievement and all the more so for having been completed in one week of around-the-clock work by scientists at Canada's National Microbiology Laboratory in Winnipeg. This is, as the saying goes, kind of a big deal.
These findings shed some intriguing light on the outbreak of H1N1 but raises even more questions, as most scientific discoveries do. For example, researchers found virtually no difference between the Mexican strains and those occurring in the US or Canada. Why, then, have so many more cases in Mexico proven fatal? The answers may not lie in the genes themselves, but rather in differences of health infrastructure and health policy. Benefits of this breakthrough include faster analysis of future strains, a better understanding of how and why H1N1 mutations or reassortments occur, and a better H1N1 vaccine - with this last being of crucial importance as major pharmaceutical companies begin the laborious process of choosing which sequences to use for their vaccines. With an improved understanding of the variations in the H1N1 genome, conserved sequences can be selected for use vaccines, resulting in a stronger, more robust protection against future infection.
Perhaps it is a little cynical, but one might consider that the timing of this announcement seems a little too convenient considering that today is the second day of the 62nd World Health Assembly, the annual meeting of the World Health Organization whose handling of the H1N1 outbreak has been criticized by many science and health professionals. Then again, maybe it is simply a case of serendipity; regardless, it is good news and that's worth remembering.
Plus, if you want to apply for the position of Viral Genome Curator at a company in Bethesda, MD, you now have one more fully-sequenced genome to add to the list.
For more information:
http://www.canada.com/Health/Canadian+completes+sequencing+virus/1569084/story.html
© A Quantum of Science / Peter Smalley (2009)
Reproduction with attribution is appreciation
Now we know the complete blueprint for H1N1; now what?
Today it was announced that scientists in Canada have fully sequenced the entire genome of the H1N1 influenza virus. While it's not the first viral genome to be fully sequenced, it is a landmark achievement and all the more so for having been completed in one week of around-the-clock work by scientists at Canada's National Microbiology Laboratory in Winnipeg. This is, as the saying goes, kind of a big deal.
These findings shed some intriguing light on the outbreak of H1N1 but raises even more questions, as most scientific discoveries do. For example, researchers found virtually no difference between the Mexican strains and those occurring in the US or Canada. Why, then, have so many more cases in Mexico proven fatal? The answers may not lie in the genes themselves, but rather in differences of health infrastructure and health policy. Benefits of this breakthrough include faster analysis of future strains, a better understanding of how and why H1N1 mutations or reassortments occur, and a better H1N1 vaccine - with this last being of crucial importance as major pharmaceutical companies begin the laborious process of choosing which sequences to use for their vaccines. With an improved understanding of the variations in the H1N1 genome, conserved sequences can be selected for use vaccines, resulting in a stronger, more robust protection against future infection.
Perhaps it is a little cynical, but one might consider that the timing of this announcement seems a little too convenient considering that today is the second day of the 62nd World Health Assembly, the annual meeting of the World Health Organization whose handling of the H1N1 outbreak has been criticized by many science and health professionals. Then again, maybe it is simply a case of serendipity; regardless, it is good news and that's worth remembering.
Plus, if you want to apply for the position of Viral Genome Curator at a company in Bethesda, MD, you now have one more fully-sequenced genome to add to the list.
For more information:
http://www.canada.com/Health/Canadian+completes+sequencing+virus/1569084/story.html
© A Quantum of Science / Peter Smalley (2009)
Reproduction with attribution is appreciation
Quantum: flu expert fears H5N1 nightmare
A QUANTUM OF SCIENCE
What happens when the lethal but less-infective H5N1 strain of influenza mingles with the relatively benign but more-infective H1N1?
Dr. Yi Guan of Hong Kong Kong University is one of the leading flu experts in the world. His claim to fame was the isolation of the SARS virus in wild civets in 2003; his recommendation to eliminate the population of captive civets may have prevented a re-emergence of SARS since then. Now he has some strong criticisms of the World Health Organization's handling of H1N1, and worries about the potential for a sharing of lethal H5N1 genes with H1N1, which has proven itself far better at spreading itself around than H5N1.
The difference between the two strains' ability to infect may be in the gene encoding hemagglutinin, the protein that helps the virus get into cells and infect them. Recently published data shows that the genetic sequence for the hemagglutinin (HA) gene is only 9.7% similar between H5N1 and H1N1, by far the largest difference between their genetic codes. Because influenza is capable of rapid reassortment - the shuffling of genes like decks of cards - it may only be a matter of time before the HA gene from H1N1 is adopted by H5N1. That could have profoundly dire effects if experts like Dr. Guan are to be believed. So far the only ray of hope that nightmare scenario will not happen is the H1N1 seems restricted to North America, while H5N1 is only found in Asia. Critics of the WHO like Dr. Guan seem to be quite justified in calling for increased attention to transcontinental spread of H1N1 and more aggressive use of TamiFlu and other treatments to curb the spread of H1N1 into Asia.
More information:
http://blogs.sciencemag.org/scienceinsider/2009/05/exclusive-meet.html
© A Quantum of Science / Peter Smalley (2009)
Reproduction with attribution is appreciation
What happens when the lethal but less-infective H5N1 strain of influenza mingles with the relatively benign but more-infective H1N1?
Dr. Yi Guan of Hong Kong Kong University is one of the leading flu experts in the world. His claim to fame was the isolation of the SARS virus in wild civets in 2003; his recommendation to eliminate the population of captive civets may have prevented a re-emergence of SARS since then. Now he has some strong criticisms of the World Health Organization's handling of H1N1, and worries about the potential for a sharing of lethal H5N1 genes with H1N1, which has proven itself far better at spreading itself around than H5N1.
The difference between the two strains' ability to infect may be in the gene encoding hemagglutinin, the protein that helps the virus get into cells and infect them. Recently published data shows that the genetic sequence for the hemagglutinin (HA) gene is only 9.7% similar between H5N1 and H1N1, by far the largest difference between their genetic codes. Because influenza is capable of rapid reassortment - the shuffling of genes like decks of cards - it may only be a matter of time before the HA gene from H1N1 is adopted by H5N1. That could have profoundly dire effects if experts like Dr. Guan are to be believed. So far the only ray of hope that nightmare scenario will not happen is the H1N1 seems restricted to North America, while H5N1 is only found in Asia. Critics of the WHO like Dr. Guan seem to be quite justified in calling for increased attention to transcontinental spread of H1N1 and more aggressive use of TamiFlu and other treatments to curb the spread of H1N1 into Asia.
More information:
http://blogs.sciencemag.org/scienceinsider/2009/05/exclusive-meet.html
© A Quantum of Science / Peter Smalley (2009)
Reproduction with attribution is appreciation
Wednesday, May 6, 2009
Down With the Sickness
A QUANTUM OF SCIENCE
Down With the Sickness,
or why you should be glad to have the flu now (as opposed to later)
Being sick is no fun. Congestion, fever, coughing – there’s nothing good about it. Or is there? For a single human being the answer may be "no" but for large groups of humans the grim reality of a multi-stage pandemic makes beating the rush a smart strategy.
First let’s talk about the adaptive immune system. Every time your body encounters a foreign protein such as a virus, your immune system kicks in and starts the process of identifying the invader, teaching other cells how to recognize it, and systematically degrading the virus wherever it is found in the body. There are many different cells involved in this process but the big players are the special white blood cells known as T-cells, B-cells, and macrophages. Just a few words about each will be sufficient for our later discussion.
T-cells mature in the thymus (hence "T") and are responsible for several important immune activities: secretion of cytokines (small chemical triggers that turn on various parts of the immune system), destruction of infected cells, and eventual suppression of immune response (if your immune system doesn't know when to turn off it eventually attacks itself). B-cells are maintained in the bone marrow (hence "B") and work by engulfing an invader, chewing it up and displaying bits and pieces of it on the cell surface. T-cells that are already on alert for the same invader bind to the B-cell and secrete cytokines telling the B-cell to multiply and mature, after which it churns out antibodies that bind to the invader and signal its destruction. B-cells that survive this process through multiple rounds are called memory B-cells and are the repository of much of humans’ adaptive immune repertoire. Finally, macrophages ("big eaters") literally swallow viral particles and even whole bacteria, digesting them and displaying bits and pieces of them in much the same way that B-cells do, eventually recruiting T-cells to flag the invader and make it easier to find and consume. A single macrophage can consume a hundred bacteria before its own digestive enzymes break it down from the inside.
Now that we now a bit more about the major players of the immune system, let’s talk about one particular invader: the influenza virus. A virus is a small bundle of proteins that can be thought of as a kind of microscopic mosquito, with long "legs" that latch onto a target cell and a dense "body" containing its own genes for making more copies of itself.
The influenza virus is a rough sphere or filament coated with proteins that bind to human cells using a protein called hemagglutinin (abbreviated HA) that works by binding to a particular sugar modification called sialic acid. Once bound, the cell "ingests" the virus in a special bubble called an endosome, the purpose of which is to isolate the virus and fuse the endosome with an acidic lysozome in order to degrade the virus down to harmless nuts and bolts. HA is specifically adapted to this use strategy against the cell, however; the acidic environment causes it to alter its shape and helps the virus escape the lysozome, where its RNA genes can be released directly into the cell and the copying process can begin. Once this happens, the cell cannot tell which RNA is viral and which is its own, so its cellular machinery begins turning viral RNA into protein – new copies of the virus – and the battle is effectively over for that cell.
The other major player for the influenza virus is called neuraminidase (NA), an enzyme that is critical for release of the many-times-copied virus out of the cell. The HA part of these copied viruses would like nothing better than to bind to the sialic acid in the cell wall once again, just as it did when entering the cell; in order to prevent that, NA cleaves the sialic acid off of sugar molecules in the cell membrane and helps the viral copies escape the cell and spread out to look for new cells to infect. Some of the most potent anti-influenza drugs currently available, including TamiFlu, specifically inhibit viral neuraminidase, a perfect target because humans do not possess that enzyme.
Because these two enzymes (hemagglutinin and neuraminidase) are so critical for the activity and pathogenicity of the influenza virus, virologists classify strains of influenza based on which versions of those two enzymes characterize that strain. There are 16 types of HA and 9 types of NA, meaning that there is a range of 144 individual influenza strains in this group. Strains of related pairings of these two enzymes compose the major classifications of the flu virus, such as the avian flu that was the specter of the 1990’s (H5N1) as well as the current strain of interest: H1N1 swine flu.
H1N1 is a subtype of the Influenza A class, and is composed of eight single-stranded RNA molecules that code for eight individual proteins. Unlike many viruses, however, these eight genes are not all part of a single long string of nucleic acid; and because they are physically separate, they lend themselves well to a process called reassortment in which a cell infected by different strains of the influenza virus will package genes from different viruses together into a new, hybrid virus. By analogy, imagine the cell as a car manufacturing plant: viral proteins are assembled into cars (viruses), all of which look pretty similar. The owner’s manual (RNA genes) that goes into each car, however, might be made up of pages taken from two different models (viral strains), so when a particular car (virus) later infects a new cell, the hybrid owner's manual it comes with gives rise to an entirely new model of car (virus). Reassortment is what allows influenza viruses from different species to commingle and generate new, more pathogenic hybrid strains of the virus, as well as helping them continue to elude the best efforts of the immune system to recognize and eradicate the virus. It also makes it difficult for scientists to predict which strain of influenza should be included in this year's flu shot. The current H1N1 model is what is known as a triple reassortment - a virus carrying genes from avian, swine and human influenza strains.
So what about the H1N1 model? Scientists are concerned about the current outbreak of H1N1 that began inMexico
So far the North American H1N1 shows no signs of being capable of creating a cytokine storm effect in its victims. So we’re home free, right? As it turns out, it’s not that simple. Researchers who have charted the progression of the 1918 epidemic show a peculiar three-stage pattern in which the H1N1 strain killed 5 people per thousand in July of 1918, then 25 per thousand in November of that year, and finally 12 per thousand in March 1919. The current scientific explanation of this pattern, based on viral RNA extracted from well-preserved victims who died at different stages of the epidemic, is that there was a critical mutation of the strain in just four brief months between the first and second emergence of the H1N1 virus. Normally when a virus gains in strength its victims are more likely to stay home and not spread it, but in late 1918 World War I was still raging, and it is theorized that the concentration of military personnel around the world fostered the spread of the more pathogenic mutant. Because the mutant was so lethal, it actually inhibited its own reproduction and thus the third emergence showed another new mutant, this one less pathogenic. By that time the war was over and sociological pressures that favored the spread of the virus were far reduced; there was no fourth emergence.
So what does this teach us regarding the current H1N1 outbreak? Quite a bit, actually. Our world today is much different than the world of 1918. Air travel can now spread a virus around the world literally overnight, exposing vast numbers of people in a far shorter span than was ever true in the crowded field hospitals and trenches of World War I. The speed at which a pandemic could take hold in many major cities around the world means the window for an effective response time is also much shorter. On the other hand, we now know about cytokine storms and how to prevent them using a variety of drugs like corticosteroids, free radical scavengers and TNF-alpha inhibitors. Further, powerful drugs like TamiFlu provide an effective answer to pandemics, especially among healthcare professionals who are on the front lines in any major public health threat. And most reassuringly of all, epidemiologists are well aware of the possibility of pandemic and are, if anything, overeager in their efforts to spread the word about that possibility. This may create some annoying overdramatization in the media, but considering that electronic media now encircle the globe far faster even than air travel, any increase in public awareness remains the first, best line of defense against a pandemic outbreak.
And one more thing about the 1918 H1N1 pandemic: those who caught the earliest, least pathogenic strain of the virus were largely immune to later mutants. So if you’re a parent thinking about keeping your child out of school, or if the guy next to you at work keeps coughing in your direction, just remember that if things go bad, you’re probably better off catching that flu now when it’s in the mildest form – just in case.
For more information:
http://www.newscientist.com/article/dn17072-first-genetic-analysis-of-swine-flu-reveals-potency.html
http://www.newscientist.com/article/dn17077-flu-outbreak-the-pig-connection.html
http://www.cnn.com/video/?/video/health/2009/04/28/am.gupta.swine.flu.model.cnn
© AQOS, Peter Smalley (2009)
Distribution with attribution is appreciation
Down With the Sickness,
or why you should be glad to have the flu now (as opposed to later)
Being sick is no fun. Congestion, fever, coughing – there’s nothing good about it. Or is there? For a single human being the answer may be "no" but for large groups of humans the grim reality of a multi-stage pandemic makes beating the rush a smart strategy.
First let’s talk about the adaptive immune system. Every time your body encounters a foreign protein such as a virus, your immune system kicks in and starts the process of identifying the invader, teaching other cells how to recognize it, and systematically degrading the virus wherever it is found in the body. There are many different cells involved in this process but the big players are the special white blood cells known as T-cells, B-cells, and macrophages. Just a few words about each will be sufficient for our later discussion.
T-cells mature in the thymus (hence "T") and are responsible for several important immune activities: secretion of cytokines (small chemical triggers that turn on various parts of the immune system), destruction of infected cells, and eventual suppression of immune response (if your immune system doesn't know when to turn off it eventually attacks itself). B-cells are maintained in the bone marrow (hence "B") and work by engulfing an invader, chewing it up and displaying bits and pieces of it on the cell surface. T-cells that are already on alert for the same invader bind to the B-cell and secrete cytokines telling the B-cell to multiply and mature, after which it churns out antibodies that bind to the invader and signal its destruction. B-cells that survive this process through multiple rounds are called memory B-cells and are the repository of much of humans’ adaptive immune repertoire. Finally, macrophages ("big eaters") literally swallow viral particles and even whole bacteria, digesting them and displaying bits and pieces of them in much the same way that B-cells do, eventually recruiting T-cells to flag the invader and make it easier to find and consume. A single macrophage can consume a hundred bacteria before its own digestive enzymes break it down from the inside.
Now that we now a bit more about the major players of the immune system, let’s talk about one particular invader: the influenza virus. A virus is a small bundle of proteins that can be thought of as a kind of microscopic mosquito, with long "legs" that latch onto a target cell and a dense "body" containing its own genes for making more copies of itself.
The influenza virus is a rough sphere or filament coated with proteins that bind to human cells using a protein called hemagglutinin (abbreviated HA) that works by binding to a particular sugar modification called sialic acid. Once bound, the cell "ingests" the virus in a special bubble called an endosome, the purpose of which is to isolate the virus and fuse the endosome with an acidic lysozome in order to degrade the virus down to harmless nuts and bolts. HA is specifically adapted to this use strategy against the cell, however; the acidic environment causes it to alter its shape and helps the virus escape the lysozome, where its RNA genes can be released directly into the cell and the copying process can begin. Once this happens, the cell cannot tell which RNA is viral and which is its own, so its cellular machinery begins turning viral RNA into protein – new copies of the virus – and the battle is effectively over for that cell.
The other major player for the influenza virus is called neuraminidase (NA), an enzyme that is critical for release of the many-times-copied virus out of the cell. The HA part of these copied viruses would like nothing better than to bind to the sialic acid in the cell wall once again, just as it did when entering the cell; in order to prevent that, NA cleaves the sialic acid off of sugar molecules in the cell membrane and helps the viral copies escape the cell and spread out to look for new cells to infect. Some of the most potent anti-influenza drugs currently available, including TamiFlu, specifically inhibit viral neuraminidase, a perfect target because humans do not possess that enzyme.
Because these two enzymes (hemagglutinin and neuraminidase) are so critical for the activity and pathogenicity of the influenza virus, virologists classify strains of influenza based on which versions of those two enzymes characterize that strain. There are 16 types of HA and 9 types of NA, meaning that there is a range of 144 individual influenza strains in this group. Strains of related pairings of these two enzymes compose the major classifications of the flu virus, such as the avian flu that was the specter of the 1990’s (H5N1) as well as the current strain of interest: H1N1 swine flu.
H1N1 is a subtype of the Influenza A class, and is composed of eight single-stranded RNA molecules that code for eight individual proteins. Unlike many viruses, however, these eight genes are not all part of a single long string of nucleic acid; and because they are physically separate, they lend themselves well to a process called reassortment in which a cell infected by different strains of the influenza virus will package genes from different viruses together into a new, hybrid virus. By analogy, imagine the cell as a car manufacturing plant: viral proteins are assembled into cars (viruses), all of which look pretty similar. The owner’s manual (RNA genes) that goes into each car, however, might be made up of pages taken from two different models (viral strains), so when a particular car (virus) later infects a new cell, the hybrid owner's manual it comes with gives rise to an entirely new model of car (virus). Reassortment is what allows influenza viruses from different species to commingle and generate new, more pathogenic hybrid strains of the virus, as well as helping them continue to elude the best efforts of the immune system to recognize and eradicate the virus. It also makes it difficult for scientists to predict which strain of influenza should be included in this year's flu shot. The current H1N1 model is what is known as a triple reassortment - a virus carrying genes from avian, swine and human influenza strains.
So what about the H1N1 model? Scientists are concerned about the current outbreak of H1N1 that began in
So far the North American H1N1 shows no signs of being capable of creating a cytokine storm effect in its victims. So we’re home free, right? As it turns out, it’s not that simple. Researchers who have charted the progression of the 1918 epidemic show a peculiar three-stage pattern in which the H1N1 strain killed 5 people per thousand in July of 1918, then 25 per thousand in November of that year, and finally 12 per thousand in March 1919. The current scientific explanation of this pattern, based on viral RNA extracted from well-preserved victims who died at different stages of the epidemic, is that there was a critical mutation of the strain in just four brief months between the first and second emergence of the H1N1 virus. Normally when a virus gains in strength its victims are more likely to stay home and not spread it, but in late 1918 World War I was still raging, and it is theorized that the concentration of military personnel around the world fostered the spread of the more pathogenic mutant. Because the mutant was so lethal, it actually inhibited its own reproduction and thus the third emergence showed another new mutant, this one less pathogenic. By that time the war was over and sociological pressures that favored the spread of the virus were far reduced; there was no fourth emergence.
So what does this teach us regarding the current H1N1 outbreak? Quite a bit, actually. Our world today is much different than the world of 1918. Air travel can now spread a virus around the world literally overnight, exposing vast numbers of people in a far shorter span than was ever true in the crowded field hospitals and trenches of World War I. The speed at which a pandemic could take hold in many major cities around the world means the window for an effective response time is also much shorter. On the other hand, we now know about cytokine storms and how to prevent them using a variety of drugs like corticosteroids, free radical scavengers and TNF-alpha inhibitors. Further, powerful drugs like TamiFlu provide an effective answer to pandemics, especially among healthcare professionals who are on the front lines in any major public health threat. And most reassuringly of all, epidemiologists are well aware of the possibility of pandemic and are, if anything, overeager in their efforts to spread the word about that possibility. This may create some annoying overdramatization in the media, but considering that electronic media now encircle the globe far faster even than air travel, any increase in public awareness remains the first, best line of defense against a pandemic outbreak.
And one more thing about the 1918 H1N1 pandemic: those who caught the earliest, least pathogenic strain of the virus were largely immune to later mutants. So if you’re a parent thinking about keeping your child out of school, or if the guy next to you at work keeps coughing in your direction, just remember that if things go bad, you’re probably better off catching that flu now when it’s in the mildest form – just in case.
For more information:
http://www.newscientist.com/article/dn17072-first-genetic-analysis-of-swine-flu-reveals-potency.html
http://www.newscientist.com/article/dn17077-flu-outbreak-the-pig-connection.html
http://www.cnn.com/video/?/video/health/2009/04/28/am.gupta.swine.flu.model.cnn
© AQOS, Peter Smalley (2009)
Distribution with attribution is appreciation
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