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  • PB1 F2 a single mutation ( HK 97 and 1918) increase virulence

    http://pathogens.plosjournals.org/pe...l.ppat.0030141







    A Single Mutation in the PB1-F2 of H5N1 (HK/97) and 1918 Influenza A Viruses Contributes to Increased Virulence

    <!-- end title area --> <!-- start authors --> Gina M. Conenello<sup>1</sup>, Dmitriy Zamarin<sup>1</sup>, Lucy A. Perrone<sup>2</sup>, Terrence Tumpey<sup>2</sup>, Peter Palese<sup>1,</sup><sup>3</sup><sup>*</sup>
    <!-- end authors --> <!-- start affiliations --> 1 Department of Microbiology, Mount Sinai School of Medicine, New York, New York, United States of America, 2 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America, 3 Department of Medicine, Mount Sinai School of Medicine, New York, New York, United States of America
    <!-- end affiliations --><!-- start: abstract --> The proapoptotic PB1-F2 protein of influenza A viruses has been shown to contribute to pathogenesis in the mouse model. Expression of full-length PB1-F2 increases the pathogenesis of the influenza A virus, causing weight loss, slower viral clearance, and increased viral titers in the lungs. After comparing viruses from the Hong Kong 1997 H5N1 outbreak, one amino acid change (N66S) was found in the PB1-F2 sequence at position 66 that correlated with pathogenicity. This same amino acid change (N66S) was also found in the PB1-F2 protein of the 1918 pandemic A/Brevig Mission/18 virus. Two isogenic recombinant chimeric viruses were created with an influenza A/WSN/33 virus background containing the PB1 segment from the HK/156/97: WH and WH N66S. In mice infected with WH N66S virus there was increased pathogenicity as measured by weight loss and decreased survival, and a 100-fold increase in virus replication when compared to mice infected with the WH virus. The 1918 pandemic strain A/Brevig Mission/18 was reconstructed with a pathogenicity-reducing mutation in PB1-F2 (S66N). The resultant 1918 S66N virus was attenuated in mice having a 3-log lower 50% lethal dose and caused less morbidity and mortality in mice than the wild-type virus. Viral lung titers were also decreased in 1918 S66N–infected mice compared with wild-type 1918 virus–infected mice. In addition, both viruses with an S at position 66 (WH N66S and wt 1918) induced elevated levels of cytokines in the lungs of infected mice. Together, these data show that a single amino acid substitution in PB1-F2 can result in increased viral pathogenicity and could be one of the factors contributing to the high lethality seen with the 1918 pandemic virus.

    <!-- end abstract --> <!-- start footnote section -->Funding. GC and DZ were partially supported by NIH/NIAID 1 T32 AI07647-Training Program: Mechanisms of Virus-Host Interactions. This work was also partially supported by National Institutes of Health grants RO1-AI8998, 1 PO1 AI058113, and UO1AI070469, and the Center for Research on Influenza Pathogenesis HHSN2662000700010C.
    Competing interests. The authors have declared that no competing interests exist.
    Editor: Yoshihiro Kawaoka, University of Wisconsin-Madison, United States of America
    Citation: Conenello GM, Zamarin D, Perrone LA, Tumpey T, Palese P (2007) A Single Mutation in the PB1-F2 of H5N1 (HK/97) and 1918 Influenza A Viruses Contributes to Increased Virulence. PLoS Pathog 3(10): e141 doi:10.1371/journal.ppat.0030141
    Received: June 7, 2007; Accepted: August 10, 2007; Published: October 5, 2007
    This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
    Abbreviations: aa, amino acid; LD<sub>50</sub>, 50% lethal dose; MDCK, Madin Darby canine kidney; MOI, multiplicity of infection; PBS, phosphate-buffered saline; PFU, plaque-forming unit
    * To whom correspondence should be addressed. E-mail: peter.palese@mssm.edu
    <!-- end footnote section --><!-- start special linking abstract - (editorial commentary/summary, author summary) --> Author Summary

    PB1-F2 is the most recently discovered protein produced by the influenza A virus. It has been previously shown that PB1-F2 is present in the mitochondria, where it induces cell death; our laboratory has demonstrated that PB1-F2 is a contributor to pathogenesis in the mouse model of infection. To study PB1-F2 further, we examined highly pathogenic strains of avian influenza virus and located an amino acid change that seemed to be associated with increased death in mice. We studied this amino acid change in PB1-F2 at position 66 in two different viruses. A recombinant virus that has a PB1 gene from an H5N1 virus was used as well as a fully reconstructed 1918 pandemic virus. In this study, we show that a mutation in PB1-F2 found in highly pathogenic influenza A virus isolates causes nonpathogenic viruses to induce disease in mice. In addition, we show that the increased pathogenicity is associated with higher levels of virus and cytokines in the lungs. We conclude that PB1-F2 does affect pathogenicity, and that position 66 seems to play an important role in contributing to the effects of PB1-F2 in the mouse model.

    <!-- end special linking abstract - editorial commentary --><!-- start: body --> Introduction

    Influenza A virus causes 300,000–500,000 deaths worldwide each year, and in pandemic years, this number can increase to 1 million (in 1957–1958 ) or as high as 50 million, as was seen in 1918–1919 [13]. More recently, H5N1 highly pathogenic avian influenza viruses have generated great concern regarding their potential to cause a pandemic. H5N1 infections in humans were seen in Hong Kong in a small outbreak in 1997 that resulted in 18 human infections and six fatalities, and since 2003, 309 human cases of H5N1 have been confirmed with a 61% fatality rate (6/1/07) [47]. Recent work on these viruses has aimed to elucidate the virulence factors that account for the severe illness observed in humans and mice [4,812].
    The viral PB1 segment is of particular interest, since, in addition to the glycoprotein genes, the PB1 gene was the only other segment that was exchanged in the pandemic viruses of 1957 and 1968 [13]. Introduction of a novel PB1 gene into the 1998 swine reassortant viruses further implicates the role of this gene in the pathogenesis of (animal) influenza [14]. Moreover, while changes in the surface glycoproteins allow the viruses to overcome the preexisting humoral immune response, they may not be solely responsible for the high virulence of the pandemic influenza viruses. In particular, the 1918 pandemic was associated with significantly higher morbidity and mortality than the subsequent pandemics [15]. Recent reconstruction of the 1918 virus has confirmed that the viral polymerase from the 1918 influenza virus is required for full pathogenicity of the recombinant 1918 virus in mice [16]. In fact, substitution of the viral polymerase genomic segments with those of the modern H1N1 strain severely attenuated the virus in mice [16]. Recent identification and characterization of a novel influenza virus protein called PB1-F2 encoded by the PB1 gene introduced a potential virulence factor that could play a role in pathogenesis of infection with pandemic influenza viruses and explain the selection of the PB1 gene in these viruses [17].
    The influenza virus PB1-F2 is a 90–amino acid (aa) protein that is associated with the induction of cell death. The protein directly permeabilizes mitochondria, resulting in the dissipation of the mitochondrial membrane potential and the release of cytochrome c [1719]. We have previously shown that PB1-F2 contributes to viral pathogenesis in the mouse model and wanted to further investigate whether the PB1-F2 proteins encoded by highly pathogenic viruses have conserved mutations in their aa sequence that are associated with pathogenicity [20]. We chose to study the PB1-F2 proteins of the Hong Kong 1997 H5N1 viruses that caused an outbreak in humans. Characterization of the isolated viruses in mice revealed that the viruses could be subdivided into three different groups based on the pathogenicity phenotype: high-virulence, intermediate-virulence, and low-virulence [21]. Further studies provided molecular correlates of pathogenicity in the high-virulence group, though such studies were not conducted for the PB1-F2 protein [22].
    Herein, we assess the contribution of the PB1-F2 protein to the pathogenicity of a highly pathogenic H5N1 virus and the 1918 pandemic strain virus. An alignment of the aa sequences of isolates from the Hong Kong 1997 H5N1 outbreak revealed that a mutation, N66S, was associated with high pathogenicity phenotype in mice. Using a recombinant A/WSN/33 virus with the PB1 segment of A/HK/156/97, we observed increased morbidity and mortality of mice infected with a virus that contained the N66S mutation. In addition, infection with the reconstructed A/Brevig Mission/18 virus, which has an S at position 66, resulted in increased pathogenicity when compared with a reconstructed A/Brevig Mission/18 virus in which position 66 was changed to N [16]. We thereby show that PB1-F2 proteins from highly virulent viruses can contribute to pathogenicity, and identify a single aa change that confers a virulent phenotype in mice.



    etc...

  • #2
    Re: PB1 F2 a single mutation ( HK 97 and 1918) increase virulence

    hmm, I remember we had a thread here:
    http://www.singtomeohmuse.com/viewto...er=asc&start=0
    I'm interested in expert panflu damage estimates
    my current links: [url]http://bit.ly/hFI7H[/url] ILI-charts: [url]http://bit.ly/CcRgT[/url]

    Comment


    • #3
      Re: PB1 F2 a single mutation ( HK 97 and 1918) increase virulence

      From the research paper cited above:

      "After comparing viruses from the Hong Kong 1997 H5N1 outbreak, one amino acid change (N66S) was found in the PB1-F2 sequence at position 66 that correlated with pathogenicity.

      snip

      Together, these data show that a single amino acid substitution in PB1-F2 can result in increased viral pathogenicity and could be one of the factors contributing to the high lethality seen with the 1918 pandemic virus."

      Interestingly, the more recent highly pathogenic H5N1 strains circulating throughout Eurasia have "N" at position 66 of the PB1-F2 protein, while the low pathogenic H5N1 and H6N1 viruses in North America have the "S" at that position.

      Just goes to show that there may be more at work in these circulating viruses than what one amino acid mutation reveals. After the HK H5N1 of 1997, this mutation seams to have disappeared, but the pathogenicity of the H5N1 virus remains largely unchanged.

      Comment


      • #4
        Re: PB1 F2 a single mutation ( HK 97 and 1918) increase virulence

        After the HK H5N1 of 1997, this mutation seams to have disappeared...
        I would have expected a successful adaptation to remain.

        What does the "N" do? Any data?

        .
        "The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation

        Comment


        • #5
          Re: PB1 F2 a single mutation ( HK 97 and 1918) increase virulence

          Public release date: 10-Oct-2007
          [ <script language="javascript" type="text/javascript"><!-- document.write('Print Article '); // --> </script>Print Article | E-mail Article<script language="javascript" type="text/javascript"><!-- document.write(' | Close Window'); // --> </script> | Close Window ]

          Contact: Nancy Wampler
          nwampler@cell.com
          617-386-2121
          Cell Press
          Protein enhances lethality of influenza virus

          Clues from the past may influence preparations for the future

          Often called the most devastating epidemic in the recorded history of the world, the 1918 influenza virus pandemic was responsible for more than 40 million deaths across the globe. The incredible lethality of the 1918 flu strain is not well understood, despite having been under intense scrutiny for many years. Now, a new study published by Cell Press in the October issue of the journal Cell Host & Microbe unravels some of the mystery surrounding the devastating 1918 pandemic and provides key information that will help prepare for future pandemics.

          It is relatively rare for an influenza virus to be virulent enough to cause death in healthy humans. Many deaths associated with influenza are caused by the combined influence of viral disease and the following secondary bacterial infection. Although the 1918 pandemic strain was one of the few influenza viruses capable of killing healthy victims on its own, the majority of fatal cases from the “Spanish Flu” can be attributed to secondary bacterial pathogens rather than primary viral disease. This important interaction between influenza viruses and bacteria is not well understood.

          Dr. Jonathan A. McCullers from the Department of Infectious Diseases at St. Jude Children’s Research Hospital in Memphis, Tennessee and colleagues examined this interaction by studying a newly discovered influenza A virus (IAV) protein, called PB1-F2. The gene encoding PB1-F2 is present in nearly all IAVs, including highly pathogenic avian IAVs that have infected humans and the IAV associated with the 1918 pandemic. “PB1-F2 was recently shown to enhance viral pathogenicity in a mouse infection model, raising questions about its effects on the secondary bacterial infections associated with high levels of influenza morbidity and mortality,” explains Dr. McCullers.

          The researchers found that expression of PB1-F2 increased the incidence of and exacerbated secondary bacterial pneumonia in a mouse model.

          Intranasal delivery of a synthetic peptide derived from a portion of PB1-F2 had the same effects. Further, an influenza virus engineered to express a version of PB1-F2 identical to that in the 1918 pandemic strain was more virulent in mice and led to more severe bacterial pneumonia, explaining in part both the unparalleled virulence of the 1918 strain and the high incidence of fatal pneumonia during the pandemic.

          The finding that PB1-F2 promotes lung pathology in primary viral infection and secondary bacterial infection also provides critical information for the future. “Given the importance of IAV as a leading cause of virus-induced morbidity and mortality year in and year out, and its potential to kill tens of millions in the inevitable pandemic that may have its genesis in the viruses currently circulating in southeast Asia, it is imperative to understand the role of PB1-F2 in IAV pathogenicity in humans and animals,” says Dr. McCullers. “These findings also reinforce the recent suggestion of the American Society for Microbiology that nations should stockpile antibiotics for the next pandemic, since many of the deaths during this event are likely to be caused by bacterial super-infections.”
          ###
          The researchers include Julie L. McAuley of Department of Infectious Diseases, St. Jude Children’s Research Hospital in Memphis; Felicita Hornung of Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases in Bethesda; Kelli L. Boyd of Animal Resources Center, St. Jude Children’s Research Hospital in Memphis; Amber M. Smith of Department of Mathematics, University of Utah in Salt Lake City; Raelene McKeon of Department of Infectious Diseases, St. Jude Children’s Research Hospital in Memphis; Jack Bennink and Jonathan W. Yewdell of Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases in Bethesda; and Jonathan A. McCullers of Department of Infectious Diseases, St. Jude Children’s Research Hospital in Memphis.

          This work was supported by the NIH (grants AI-66349 and AI-54802), the NIAID intramural research program, and the American Lebanese Syrian Associated Charities (ALSAC).

          McAuley et al.: “Expression of the 1918 Influenza A Virus PB1-F2 Enhances the Pathogenesis of Viral and Secondary Bacterial Pneumonia.” Publishing in Cell Host & Microbe 2, 240–249, October 2007. DOI 10.1016/j.chom.2007.09.001 www.cellhostandmicrobe.com

          http://www.eurekalert.org/pub_releas...-pel100407.php
          "In the beginning of change, the patriot is a scarce man (or woman https://flutrackers.com/forum/core/i...ilies/wink.png), and brave, and hated and scorned. When his cause succeeds, the timid join him, for it then costs nothing to be a patriot."- Mark TwainReason obeys itself; and ignorance submits to whatever is dictated to it. -Thomas Paine

          Comment


          • #6
            Re: PB1 F2 a single mutation ( HK 97 and 1918) increase virulence

            These are different articles. It took my lay-person mind quite a bit to figure out what was going on.

            Is there an extremely concise summary of the current genetics research on this subject?

            I'm thinking of something like 20 statements each of which is no more than 25 words with links to the abstracts.

            Or perhaps something like a Supercourse lecture or powerpoint with each paper restricted to one slide.

            (My brief review of the Supercourse site revealed hardly anything on avian, pandemic, H5N1 etc. Is there another "open source" site for Epi lectures? Is there an FT team interested in constructing a Supercourse lecture?)

            J.

            Comment


            • #7
              Re: PB1 F2 a single mutation ( HK 97 and 1918) increase virulence

              current swine flu has a nonfunctional PB1-F2 (2 stop-amino-acids)
              while the related swine viruses with the human PB1 since 1998
              don't have stops
              I'm interested in expert panflu damage estimates
              my current links: [url]http://bit.ly/hFI7H[/url] ILI-charts: [url]http://bit.ly/CcRgT[/url]

              Comment


              • #8
                Re: PB1 F2 a single mutation ( HK 97 and 1918) increase virulence

                Could you present that info with the same terms as the above paper, ie., is position 66 "S" or "N"? Do you have confirmation you can present?

                .
                "The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation

                Comment


                • #9
                  Re: PB1 F2 a single mutation ( HK 97 and 1918) increase virulence

                  I tried to read the PB1 sequences myself on PubMed at
                  http://www.ncbi.nlm.nih.gov/nuccore/FJ981616

                  If I counted right, there is neither an "N" or "S" at position 66. See extracted info below. Am I counting correctly? Now I remember why I didn't start trying to read these a few years ago - too confusing.

                  LOCUS FJ981616 2274 bp cRNA linear VRL 01-MAY-2009 DEFINITION Influenza A virus (A/Texas/04/2009(H1N1)) segment 2 polymerase PB1 (PB1) gene, complete cds; and nonfunctional PB1-F2 protein (PB1-F2) gene, complete sequence. ……

                  CDS 1..2274 /gene="PB1" /codon_start=1 /product="polymerase PB1" /protein_id="ACQ55362.1" /db_xref="GI:229299523" /translation=

                  ="MDVNPTLLFL
                  KIPAQNAIST
                  TFPYTGDPPY
                  SHGTGTGYTM
                  DTVNRTHQYS
                  EKGKWTTNTE
                  TGAPQLNPID……

                  .
                  "The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation

                  Comment


                  • #10
                    Re: PB1 F2 a single mutation ( HK 97 and 1918) increase virulence

                    PB1-F2:

                    Code:
                     3 MEQEQDTPWTQ}TEHTNTQKRESGRQTQRLVHPSSTRLMDHYLRIMNQVGMHKQTVF}RLWLSLKNPTQEYLRIHALKQWKLFNKQG}      >A/California/04-cx/2009-04-01,10m
                     0 MEQEQDTPWTQSTEHTNIQKRGSGRQTQRLGHPSSTRLMDHYLRIMNQVDMHKQTVFWRPWLSLKNPTQGYLRIHALKQWKLFNKQGWIN}  H H1N1/  A/Wisconsin/10/98(H1N1)
                     0 MGQEQDTPWILSTGHISTQKREDGQQTPRLEHHNSTRLMDHCQKTMNQVVMPKQIVYWKQWLSLRSPTPVSLKTRVLKRWRLFSKHEWTS}  H H1N1/  A/Brevig Mission/18(H1N1)
                    
                    ....................................................................x
                    
                     0 MEQEQDTPWTQSTEHTNIQKKENGRQTQRLGHPSSTRLMDHYLKIMNQVDMHKQTVSWKPWLSLKNPTQGYLRIHALKQWKLSNKQGWIN}  >A/swine/Minnesota/SG-00241/2007(H1N1)
                     0 MEQEQDTPWTQSTEHTNIQKKGNGRQIQRLGHPSSIRLMDHYLKIMNQVDMHKQTVSWRPWLSLKNPTQGYLRIHALKQWKLSNKQGWIN}  >A/swine/OH/511445/2007(H1N1)
                     0 MEQEQDTPWTQSTEHTNIQKKGNGRQIQRLGHPSSIRLMDHYLKIMNQVDMHKQTVSWRPWLSLRNPTQGYLRIHALKQWKLSNKQGWIN}  >A/swine/Illinois/SG-00244/2007(H1N1)
                     0 MEQEQDTPWTQSTEHTNIQKKGNGRQIQRLGHPSSIRLMDHYLKIMNQVDMHKQTVSWRPWLSLKNPTQGYLRIHALKQWKLSNKQGWIN}  >A/swine/Ohio/24366/07(H1N1)
                     0 MEQEQDTLWTQSTEHTNIQKKGNGRQTQRLGHPSSTRLMDHYLKIMNQVDMHKQTVSWRPWLSLKSPTQGYLRIHALKQWKLSNKQGWIN}  >A/swine/Ohio/C62006/06(H1N1)
                     0 MEQEQDTPWTQSTEHTNTQKKGNGRQTQKLGHPSSTRLMDHYLRIMNQVDTHKQTVSWRPWLSLKNPTQGYLRIHALKQWKLSNKQGWIN}  >A/swine/Minnesota/SG-00240/2007(H1N1)
                     0 MEQEQDTPWTQSTEHINIQKKGSGLQTQRLGHPSSTRLMDHYLRIMNQVDMHKQTVFWRPWLSLKNPTQGYLRIHALKQWKLFNKQGWIN}  >A/Iowa/CEID23/2005(H1N1)
                     0 MEQEQDTPWTQSTEHTNIQKRGSGRQTQRLGHPSSTRLMDHYLRIMNQVDMHKQTVFWRPWLSLKNPTQGYLRIHALKQWKLFNKQGWIN}  >A/Wisconsin/10/98(H1N1)
                     2 MEQEQDTPWTQ}TEHTNTQKRESGRQTQRLVHPSSTRLMDHYLRIMNQVGMHKQTVF}RLWLSLKNPTQEYLRIHALKQWKLFNKQG}IN}  >A/California/04/2009-04-01/(H1N1)
                     0 MEQEQDTPWTQSTEHTNIQKKGNGRQTQRLGHPSSTRLMDHYLRIMNQVGMHKQTVSWRPWLSLKNPTQGYLRVHALKQWKLSNKQGWIN}  >A/swine/Minnesota/SG-00238/2006(H1N1)
                     0 ------------------------------------------------------------ML-----------------------------  >A/Turkey/MO/24093/99(H1N2)
                     0 MEQEQDTPWTQSTEHTNIQKKGSGRQTQRLGHPSSTRLMDHYLRIMNQVDMHKQTVFWRPWLSLKNPTQGYLRIHALKQWKLFNKQGWIN}  >A/mallard duck/South Dakota/Sg-00125/2007(H3N2)
                    I'm interested in expert panflu damage estimates
                    my current links: [url]http://bit.ly/hFI7H[/url] ILI-charts: [url]http://bit.ly/CcRgT[/url]

                    Comment


                    • #11
                      Re: PB1 F2 a single mutation ( HK 97 and 1918) increase virulence

                      I don't know, where position 66 is and how they count.
                      ------edit-----------
                      OK, I marked the position above. The 1918 virus and one Ohio swine
                      from 2006 had an N66S. The new virus has N, but it is nonfunctional
                      anyway. 3 mutations needed plus th N->S one, and mutations in PB1
                      affect the other reading frame too, so are rarer.
                      Of course, one reassortment would do it in one step ....
                      ---------------------


                      This is an overlapping reading frame in PB1, the same
                      amino acids here are differently encoded in PB1 and
                      fulfil some other task there.

                      you can see 3 stop-codons in the new virus, so the protein
                      can't be assembled.

                      If these codons mutate, they may also change the PB1-proteins
                      or are synonymous - I haven't yet checked


                      But as you can see the other normal swine viruses do have this protein.
                      What function does it have here ?



                      > PB1-F2 protein (induces apoptosis)
                      says Wikipedia

                      see also this article:
                      http://www.virologyj.com/content/pdf/1743-422x-4-9.pdf
                      I'm interested in expert panflu damage estimates
                      my current links: [url]http://bit.ly/hFI7H[/url] ILI-charts: [url]http://bit.ly/CcRgT[/url]

                      Comment


                      • #12
                        Re: PB1 F2 a single mutation ( HK 97 and 1918) increase virulence

                        comparing the PB1-F2 from 1918 and from 2009

                        first line: nucleotides (partial)
                        2nd line: main reading frame encoding the long protein PB1
                        3rd line: PB1-F2 reading frame encoding the short protein PB1-F2

                        protein encoding stops when a "}" is found

                        3 mutations are needed, which were synonymous in PB1, to undo the 3 stops,
                        but even then it seems unlikely that the encoded protein could fulfil its task and act as a
                        PB1-F2 in other human viruses.
                        But there is still the possibility to acquire a whole new PB1 by reassortment.

                        Presumably the PB1-F2 became nonfunctional years ago in Mexican swine and this
                        can't so easily be undone now in humans - except by reassortment.



                        Code:
                        
                        
                        >A/California/04/2009-04-01/(H1N1)
                        
                                                           C                                                                                                                                         G                       g                                                                  G
                        CATGGAACAGGAACAGGATACACCATGGACACAGTAAACAGAACACACCAATACTCAGAAAAGGGAAAGTGGACGACAAACACAGAGACTGGTGCACCCCAGCTCAACCCGATTGATGGACCACTACCTGAGGATAATGAACCAAGTGGGTATGCACAAACAGACTGTGTTCTAGAGGCTATGGCTTTCCTTGAAGAATCCCACCCAGGAATATTTGAGAATTCATGCCTTGAAACAATGGAAGTTGTTCAACAAACAAGGGTAGATAAACTAAC
                         H  G  T  G  T  G  Y  T  M  D  T  V  N  R  T  H  Q  Y  S  E  K  G  K  W  T  T  N  T  E  T  G  A  P  Q  L  N  P  I  D  G  P  L  P  E  D  N  E  P  S  G  Y  A  Q  T  D  C  V  L  E  A  M  A  F  L  E  E  S  H  P  G  I  F  E  N  S  C  L  E  T  M  E  V  V  Q  Q  T  R  V  D  K  L  T
                          M  E  Q  E  Q  D  T  P  W  T  Q  }  T  E  H  T  N  T  Q  K  R  E  S  G  R  Q  T  Q  R  L  V  H  P  S  S  T  R  L  M  D  H  Y  L  R  I  M  N  Q  V  G  M  H  K  Q  T  V  F  }  R  L  W  L  S  L  K  N  P  T  Q  E  Y  L  R  I  H  A  L  K  Q  W  K  L  F  N  K  Q  G  }  I  N  }    
                        
                        
                        >A/Brevig Mission/1/1918(H1N1)
                        CATGGGACAGGAACAGGATACACCATGGATACTGTCAACAGGACACATCAGTACTCAGAAAAGGGAAGATGGACAACAAACACCGAGACTGGAGCACCACAACTCAACCCGATTGATGGACCACTGCCAGAAGACAATGAACCAAGTGGTTATGCCCAAACAGATTGTGTATTGGAAGCAATGGCTTTCCTTGAGGAGTCCCACCCCGGTATCTTTGAAAACTCGTGTCTTGAAACGATGGAGGTTGTTCAGCAAACACGAGTGGACAAGCTGACGCAAGGCCGACAGACCTATGACTGGACTCTAAATAGGAACC
                         H  G  T  G  T  G  Y  T  M  D  T  V  N  R  T  H  Q  Y  S  E  K  G  R  W  T  T  N  T  E  T  G  A  P  Q  L  N  P  I  D  G  P  L  P  E  D  N  E  P  S  G  Y  A  Q  T  D  C  V  L  E  A  M  A  F  L  E  E  S  H  P  G  I  F  E  N  S  C  L  E  T  M  E  V  V  Q  Q  T  R  V  D  K  L  T  
                          M  G  Q  E  Q  D  T  P  W  I  L  S  T  G  H  I  S  T  Q  K  R  E  D  G  Q  Q  T  P  R  L  E  H  H  N  S  T  R  L  M  D  H  C  Q  K  T  M  N  Q  V  V  M  P  K  Q  I  V  Y  W  K  Q  W  L  S  L  R  S  P  T  P  V  S  L  K  T  R  V  L  K  R  W  R  L  F  S  K  H  E  W  T  S  }
                                                                                                                                                                                                                             66
                        I'm interested in expert panflu damage estimates
                        my current links: [url]http://bit.ly/hFI7H[/url] ILI-charts: [url]http://bit.ly/CcRgT[/url]

                        Comment


                        • #13
                          Re: PB1 F2 a single mutation ( HK 97 and 1918) increase virulence

                          Originally posted by cartski View Post
                          These are different articles. It took my lay-person mind quite a bit to figure out what was going on.

                          Is there an extremely concise summary of the current genetics research on this subject?

                          I'm thinking of something like 20 statements each of which is no more than 25 words with links to the abstracts.

                          Or perhaps something like a Supercourse lecture or powerpoint with each paper restricted to one slide.

                          (My brief review of the Supercourse site revealed hardly anything on avian, pandemic, H5N1 etc. Is there another "open source" site for Epi lectures? Is there an FT team interested in constructing a Supercourse lecture?)

                          J.
                          Here is a supercourse for epidemiology:

                          http://www.pitt.edu/~super1/

                          The most recent lecture concerns the current H1N1 outbreak.
                          Separate the wheat from the chaff

                          Comment


                          • #14
                            Re: PB1 F2 a single mutation ( HK 97 and 1918) increase virulence

                            Originally posted by Farmer View Post
                            Here is a supercourse for epidemiology:

                            http://www.pitt.edu/~super1/

                            The most recent lecture concerns the current H1N1 outbreak.

                            Thanks. I went through the lecture.

                            Slides 7 and 49 were interesting.

                            However, I felt that the rest of the lecture needed more work, or rather, the advice of a good editor or communications expert. Although I liked having all the info in one document, it seemed hastily cobbled together and somewhat inconsistent. Likely it's a very stressful time for the authors.

                            J.

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                            • #15
                              Re: PB1 F2 a single mutation ( HK 97 and 1918) increase virulence

                              from 1918 to 1947 H1N1 had a full PB1-F2, then since 1947 it
                              has a truncated PB1-F2 of length 57, so no mutation
                              at position 66 possible.

                              http://knol.google.com/k/vladimir-tr...b1-f2-protein/

                              1947 was a severe season with a new variant appearing
                              and a total vaccine failure. Almost a pandemic but
                              mortality was low.
                              I remember a paper about reassortments in 1947(and 1951).

                              The truncated PB1-F2 had appeared after that ?
                              I think A/Fort Monmouth/1947(H1N1) was the pseudo-pandemic
                              strain and it had the full PB1-F2.

                              So...maybe rather than ****** acquiring the full PB1-F2
                              from seasonal H3N2, H3N2 may get the PB1 from ******
                              and become less virulent...
                              Has it been tested ?
                              I'm interested in expert panflu damage estimates
                              my current links: [url]http://bit.ly/hFI7H[/url] ILI-charts: [url]http://bit.ly/CcRgT[/url]

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