Reasonable Rascal
01-19-02, 12:59
Date: Fri 18 Jan 2002
From: ProMED-mail <promed@promedmail.org>
Source: Newsday.com, Tue 15 Jan 2002 [edited]
http://www.newsday.com/news/printedition/health/ny-dsbelow2551849jan15.story?coll=ny%2Ddiscovery%2Dpr int
11th influenza virus protein may play role in virulence
---------------------------------------------
An international team of researchers has discovered a new protein [PB1-F2] that could explain why some types of influenza are far more deadly than others. The discovery may finally answer why some influenza outbreaks, especially the worldwide influenza pandemic of 1918, became exceptionally lethal. And it may also explain why influenza viruses that come to us from birds are especially bad.
The 1918 flu pandemic was extraordinary because it spread very rapidly worldwide and killed 20 million to 40 million people. Oddly, a large percentage of its victims were young adults, who can usually survive flu.
According to immunologist Jonathan Yewdell, all that is known about the new virus protein is that it is made in an odd way [by translation from an alternate reading frame] and that it seems especially adept at killing immune system cells called monocytes. It seems to work by [damaging] mitochondria, the cell's internal energy-making bodies.
In their report in a recent issue of Nature Medicine [see below], Yewdell and his colleagues said "a possible clue to the involvement of PB1-F2 in influenza A virus pathogenicity" may come from data showing that the gene itself apparently came from a bird virus. That fits with what was seen in a highly dangerous influenza outbreak in Hong Kong in 1997, caused by a virus that got into humans directly from chickens. "Our discovery was completely serendipitous," Yewdell said. "We were looking for bits of proteins that
are recognized by T-cells, the specialized white blood cells that attack viruses. We were screening to see if any "junk peptides" [useless protein fragments] were made by the virus genes. We found one, and we wanted to make sure it was really junk. But instead it was one with a real function."
Yewdell and 8 of his co-authors work at the National Institute of Allergy and Infectious Diseases, in Bethesda, Maryland; 2 other team members work in Hamburg, Germany, and another is at the Mount Sinai School of Medicine in Manhattan. Years of study had already shown that the influenza virus carries just 8 genes, and that these genes combine to make just 10 proteins, enough to let the virus infect cells, reproduce itself, and then escape to infect other cells. Now it seems there are 11 proteins, and perhaps even more yet to be discovered. Unlike most proteins, each of which is made by a specific gene, [the PB1-F2 protein is made by translation from an alternate reading frame in the PB-1 gene]. This new protein provides the virus with a mechanism to kill off monocytes, which protect the body against a viral infection. As the monocytes die off, the person infected by the influenza virus has less and less ability to fight off the virus attack. That could explain the extra-high death toll associated with some strains of influenza virus.
[Byline: Robert Cooke]
--
ProMED-mail
<promed@promedmail.org>
[There have been several fruitless attempts to establish the basis for the exceptional severity of the influenza epidemic of 1918. Whether the PB1-F2 protein described above was a determining factor remains to be established, although its apparent derivation from an avian influenza virus is suggestive. The mitochondrial localization of the protein may or may not be fortuitous.
The reference for the original paper is as follows: Chen W, Calvo PA, Malide D, Gibbs J, Schubert U, Bacik I, et al. A novel influenza A virus mitochondrial protein that induces cell death. Nature Medicine 2001; 7: 1306-12
<http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v7/n12/abs/nm1201-1306.html>.
The abstract describes the general properties of the PB1-F2 protein as follows: "While searching for alternative reading-frame peptides encoded by influenza A virus that are recognized by CD8+ T cells, we found an abundant immunogenic peptide encoded by the +1 reading frame of PB1. This peptide derives from a novel conserved 87-residue protein, PB1-F2, which has several unusual features compared with other influenza gene products in addition to its mode of translation. These include its absence from some animal (particularly swine) influenza virus isolates, variable expression in individual infected cells, rapid proteasome-dependent degradation and mitochondrial localization. Exposure of cells to a synthetic version of PB1-F2 induces apoptosis, and influenza viruses with targeted mutations that interfere with PB1-F2 expression induce less extensive apoptosis in human monocytic cells than those with intact PB1-F2. We propose that PB1-F2 functions to kill host immune cells responding to influenza virus infection." -
---------------------------------------------
In layman's terms there is such a thing as a "superflu" such as was seen in 1918, and again with the swine flu a couple decades past, though due to modern medicine and a bit of luck (divine intervention?) that one was not nearly so bad as the Spanish Flu.
Historically superflues occur over semi-regular periods, interspersed with other infectious disease outbreaks that seem to sweep the population. While these occur regularly throughout the world in other countries we seldom see much mention in the media. Currently there is an Ebola oubreak affecting dozens of cases (so far) in the Gabon/Congo area. it is bad enough that the medical teams sent to the area pulled out for a time but are considering going back.
As far as the US is concerned we are overdue for an epidemic, and the world in general for a pandemic, such as was the Spanish Flu. Far reaching, crossing boarders, and a high mortality. Keep in mind we have never yet cured any virus-borne disease, we can only manage symptoms to varying degrees.
RR
From: ProMED-mail <promed@promedmail.org>
Source: Newsday.com, Tue 15 Jan 2002 [edited]
http://www.newsday.com/news/printedition/health/ny-dsbelow2551849jan15.story?coll=ny%2Ddiscovery%2Dpr int
11th influenza virus protein may play role in virulence
---------------------------------------------
An international team of researchers has discovered a new protein [PB1-F2] that could explain why some types of influenza are far more deadly than others. The discovery may finally answer why some influenza outbreaks, especially the worldwide influenza pandemic of 1918, became exceptionally lethal. And it may also explain why influenza viruses that come to us from birds are especially bad.
The 1918 flu pandemic was extraordinary because it spread very rapidly worldwide and killed 20 million to 40 million people. Oddly, a large percentage of its victims were young adults, who can usually survive flu.
According to immunologist Jonathan Yewdell, all that is known about the new virus protein is that it is made in an odd way [by translation from an alternate reading frame] and that it seems especially adept at killing immune system cells called monocytes. It seems to work by [damaging] mitochondria, the cell's internal energy-making bodies.
In their report in a recent issue of Nature Medicine [see below], Yewdell and his colleagues said "a possible clue to the involvement of PB1-F2 in influenza A virus pathogenicity" may come from data showing that the gene itself apparently came from a bird virus. That fits with what was seen in a highly dangerous influenza outbreak in Hong Kong in 1997, caused by a virus that got into humans directly from chickens. "Our discovery was completely serendipitous," Yewdell said. "We were looking for bits of proteins that
are recognized by T-cells, the specialized white blood cells that attack viruses. We were screening to see if any "junk peptides" [useless protein fragments] were made by the virus genes. We found one, and we wanted to make sure it was really junk. But instead it was one with a real function."
Yewdell and 8 of his co-authors work at the National Institute of Allergy and Infectious Diseases, in Bethesda, Maryland; 2 other team members work in Hamburg, Germany, and another is at the Mount Sinai School of Medicine in Manhattan. Years of study had already shown that the influenza virus carries just 8 genes, and that these genes combine to make just 10 proteins, enough to let the virus infect cells, reproduce itself, and then escape to infect other cells. Now it seems there are 11 proteins, and perhaps even more yet to be discovered. Unlike most proteins, each of which is made by a specific gene, [the PB1-F2 protein is made by translation from an alternate reading frame in the PB-1 gene]. This new protein provides the virus with a mechanism to kill off monocytes, which protect the body against a viral infection. As the monocytes die off, the person infected by the influenza virus has less and less ability to fight off the virus attack. That could explain the extra-high death toll associated with some strains of influenza virus.
[Byline: Robert Cooke]
--
ProMED-mail
<promed@promedmail.org>
[There have been several fruitless attempts to establish the basis for the exceptional severity of the influenza epidemic of 1918. Whether the PB1-F2 protein described above was a determining factor remains to be established, although its apparent derivation from an avian influenza virus is suggestive. The mitochondrial localization of the protein may or may not be fortuitous.
The reference for the original paper is as follows: Chen W, Calvo PA, Malide D, Gibbs J, Schubert U, Bacik I, et al. A novel influenza A virus mitochondrial protein that induces cell death. Nature Medicine 2001; 7: 1306-12
<http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v7/n12/abs/nm1201-1306.html>.
The abstract describes the general properties of the PB1-F2 protein as follows: "While searching for alternative reading-frame peptides encoded by influenza A virus that are recognized by CD8+ T cells, we found an abundant immunogenic peptide encoded by the +1 reading frame of PB1. This peptide derives from a novel conserved 87-residue protein, PB1-F2, which has several unusual features compared with other influenza gene products in addition to its mode of translation. These include its absence from some animal (particularly swine) influenza virus isolates, variable expression in individual infected cells, rapid proteasome-dependent degradation and mitochondrial localization. Exposure of cells to a synthetic version of PB1-F2 induces apoptosis, and influenza viruses with targeted mutations that interfere with PB1-F2 expression induce less extensive apoptosis in human monocytic cells than those with intact PB1-F2. We propose that PB1-F2 functions to kill host immune cells responding to influenza virus infection." -
---------------------------------------------
In layman's terms there is such a thing as a "superflu" such as was seen in 1918, and again with the swine flu a couple decades past, though due to modern medicine and a bit of luck (divine intervention?) that one was not nearly so bad as the Spanish Flu.
Historically superflues occur over semi-regular periods, interspersed with other infectious disease outbreaks that seem to sweep the population. While these occur regularly throughout the world in other countries we seldom see much mention in the media. Currently there is an Ebola oubreak affecting dozens of cases (so far) in the Gabon/Congo area. it is bad enough that the medical teams sent to the area pulled out for a time but are considering going back.
As far as the US is concerned we are overdue for an epidemic, and the world in general for a pandemic, such as was the Spanish Flu. Far reaching, crossing boarders, and a high mortality. Keep in mind we have never yet cured any virus-borne disease, we can only manage symptoms to varying degrees.
RR