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  • List of Mutations

    I'm searching for the amino acid, nucleotide coding and what each one does and what segment it's found in. Any help with this would be much appreciated.

    Phenotype Marker from GenBank (** Panflu common markers)

    Segments:
    PB2(1) PB1(2) PA(3) HA(4) NP(5) NA(6) MP(7) NS(8)

    Adamatane Resistance
    M2: 26F
    M2: 27A
    M2: 30T
    M2: S31N **
    M2: 34E

    Oseltamivir Resistance
    NA: H275Y (C823T)

    Enhanced Transmission
    M2: A16G
    M2: C55F **
    NP: L136M
    PA: S409N **
    PB2: A199S
    PB2: A661T
    PB2: K702R
    PB2: V667I

    Increased Virulence
    PB2: D701N
    PB2: E627K

    Severity
    NS1:T92E

    Polybasic HA Cleavage (gs: only for H5 and H7)
    RERRRKKR

    Other H1N1 mutations we are watching:
    PB2: K340N (A1020T)
    HA: D225N (715A), D225G (716G), D225E (717A or G)
    HA: M230 730, 730, 732 ATG; M230I = AT(t,c,a?)

    When cross-linked and possibly associated with mutations at 225
    HA: syn413K (A1281G)
    NA: syn407V (T1221C)

    Segments:
    PB2(1) PB1(2) PA(3) HA(4) NP(5) NA(6) MP(7) NS(8)

    What group for these?: A193T, S193F, (HA in H3N2 ?)

    PB2: A199S, A661T, E627K, V667I, D701N, K702R,

    PB1:

    PA:

    HA: D225N, D225G, I324V

    NP:

    NA: E119V, R152K, H274Y, R292K

    MP:

    NS:

    Further explanation about resistance: the amino acid termed E276 must rotate and bond with R224 to form a pocket for the side chain of Oseltamivir. The mutations R292K, N294S, and H274Y inhibit this rotation and prevent the pocket from forming, resulting in resistance to Oseltamivir. An E119V mutation also interferes only with oseltamivir binding, possibly because a water molecule can fit between oseltamivir and valine at the active site but cannot insinuate itself between zanamivir and valine at residue 119.
    Pharmacological profile and review regarding Tamiflu, (oseltamivir) - indications and side effects.
    The salvage of human life ought to be placed above barter and exchange ~ Louis Harris, 1918

  • #2
    Re: List of Mutations

    Here are the amino acids:

    A: GCT, GCC, GCA, GCG (Alanine,Ala)
    R: CGT, CGC, CGA, CGG, AGA, AGG (Arginine,Arg)
    N: AAT, AAC (Asparagine,Asn)
    D: GAT, GAC (Aspartic Acid,Asp)
    C: TGT, TGC (Cysteine,Cys)
    E: GAA,GAG (GlutamicAcid,Glu)
    Q: CAA,CAG (Glutamine,Gln)
    G: GGT, GGC, GGA, GGG (Glycine,Gly)
    H: CAT, CAC (Histidine,His)
    I: ATT, ATC, ATA (Isoleucine,Ile)
    L: TTA, TTG, CTT, CTC, CTA, CTG (Leucine,Leu)
    K: AAA, AAG (Lysine,Lys)
    M: ATG (Methionine,Met)
    F: TTT, TTC (Phenylalanine,Phe)
    P: CCT, CCC, CCA, CCG (Proline,Pro)
    S: TCT, TCC, TCA, TCG, AGT, AGC (Serine,Ser)
    T: ACT, ACC, ACA, ACG (Threonine,Thr)
    W: TGG (Tryptophan,Trp)
    Y: TAT, TAC (Tyrosine,Tyr)
    V: GTT, GTC, GTA, GTG (Valine,Val)

    STOP,Sto,}: TAG, TGA, TAA
    hydrophobic: GAVLIMFWP
    hydrophilic:
    STCYNQ,DE,KRH

    ATG, ATT, ATC, ATA, AAA, AAG, AAT, AAC, ACT, ACC, ACA, ACG, AGA, AGG, AGT, AGC
    CAA, CAG, CAT, CAC, CCT, CCC, CCA, CCG, CGT, CGC, CGA, CGG, CTT, CTC, CTA, CTG
    GCT, GCC, GCA, GCG, GAT, GAC, GAA, GAG, GGT, GGC, GGA, GGG, GTT, GTC, GTA, GTG
    TAT, TAC, TGT, TGC, TTA, TTG, TTT, TTC, TCT, TCC, TCA, TCG, TGG, TAG, TGA, TAA
    The salvage of human life ought to be placed above barter and exchange ~ Louis Harris, 1918

    Comment


    • #3
      Re: List of Mutations

      glycosylation positions:
      21, 33, 63, 81, 94, 129, 158, 163, 271, 289, 154

      receptor binding sites
      98,134-138,153-155,184-196,216-230 (H3)

      Here's the list of mutations Gs made; it can also be updated.

      PB2(1) PB1(2) PA(3) HA(4) NP(5) NA(6) MP(7) NS(8)

      PB2: G0546A, G0799A, A1218G, G1308A, A1577G, T1711C, G1945A, A2030G, G2163A
      PB1: A0300G, T0450C, G0636A, A1058G, T2000C
      PA: A0008G, A0561C, A0588G, G0936A, A1741C, G1986T,
      HA: C0022A, C0145A, T0658A, G0687T, A0877G, G1173A, C1408T, G1563A
      NP: C0132T, G0298A, C1118T, G1143A, G1248A,
      NA: A0283G, G0316A, A0742G, A1044G
      MP: G0492A, G0522A, G0600A,
      NS: A0367G, G0658A, C0738A, A0775G

      ------------------------------

      their S224P in PA is my T670C(3)
      M582L in PA is A1741C(3)
      S91P in HA is T298C(4)
      S206T in HA is T658A(4)
      V323I in HA is G1012A(4)
      V100I in NP is G298A(5)
      T373I in NP is C1118T(5)
      V106I in NA is G316A(6)
      N247D in NA is A742G(6)


      so their variant i is my "early Mex"
      their variant ii is my "Northern"
      their varint iii is my "pre-Cancun"
      their variant iv is my "Cancun"
      their variant v is my "early US" (they don't include Texas/15 here)
      The salvage of human life ought to be placed above barter and exchange ~ Louis Harris, 1918

      Comment


      • #4
        Re: List of Mutations

        As provided by Mamabird here:

        Provided in 1, below are the problem amino acids associated with the currently circulating Swine Flu. These are generally found in every pandemic virus and most seasonal flu viruses, and some relate to sensitivity to antivirals, etc. All the available Swine Flu virus gene sequences have these human/problem characteristics.

        1. PB2: A199S; PB1 N(T)375S; PB1-F2 P(R)48Q; PA T129I and S409N; HA E190D, S221P, F251L and Y258F; NP V33I, R100V and Q357K; MP K27R, I168T and N224S; M2 none; NS2 F55L; NA none.

        Provided in 2, below are those amino acids that this bug has not yet obtained, but if obtained, could be problematic. Some are more important that others. None of the Swine Flu viruses have these characteristics as far as I know, but we should all keep an eye out for them>

        2. PB2 L(F)475M, D567N and E627K; PB1 none; PB1-F2 P28L, D55N, I(V)100A and T552S; HA multi-basic amino acids at the clevage site (usually associated only with poultry infections); NP G16D, L283P and F313Y; MP I15V, K101R, A166V and N207S; M2 E16G and S20N; NS none; NS2 none; NA H274Y and N294S.

        In other words, the Swine Flu virus has about half of the problem amino acids already in its tool box. The only other viruses even close to this are some H9N2 viruses circulating widely in Hong Kong and H7N7 in the Netherlands. As to the wild type avian viruses, only the North American variety come close.

        Take away: This is a problem virus that bears watching closely. Reassortment with seasonal flu or H5N1 could be interesting.

        .
        "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: List of Mutations

          Toaster2 added this later in that thread:

          HA I219K should be associated with increased transmission by droplets
          .
          "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


          • #6
            Re: List of Mutations

            Originally posted by mixin View Post
            hydrophobic: GAVLIMFWP
            hydrophilic:
            STCYNQ,DE,KRH
            GAVLIMFWP Nonpolar, hydrophobic
            STCYNQ Polar, hydrophilic
            DE Acidic, hydrophilic
            KRH Basic, hydrophilic
            </pre>

            Comment


            • #7
              Re: List of Mutations

              In Mamabird's post, she has an extra letter in parentheses. Why?

              L(F)475M ... I(V)100A
              The salvage of human life ought to be placed above barter and exchange ~ Louis Harris, 1918

              Comment


              • #8
                Re: List of Mutations

                Originally posted by Sally View Post
                GAVLIMFWP Nonpolar, hydrophobic
                STCYNQ Polar, hydrophilic
                DE Acidic, hydrophilic
                KRH Basic, hydrophilic
                </pre>
                Can you tell us why these are important?
                The salvage of human life ought to be placed above barter and exchange ~ Louis Harris, 1918

                Comment


                • #9
                  Re: List of Mutations

                  the 1918-virus had 46=8+7+10+9+7+5 amino-acid mutations in the
                  inner 6 segments away rom the bird-index.

                  (to compare: 1930 swine had 116,1933 human had 115,1977 swine had 180,
                  pan1957 had 123,pan1968 had 147,H3N2(2007)had 249,H1N1(2007) had 194,
                  US-swine triple-reassortant(1998) ha 107=12+15+10+26+10+34
                  pan2009 had 147=17+23+17+28+16+46, (+5+8+7+2+--+--+12 since triple-)

                  here are those 46 with a count, how often they were maintained
                  in my database of 52 viruses, mainly early human and swine:

                  A199S(1),50
                  C241Y(3),49
                  D209N(8),48
                  D55N(3),44
                  D567N(1),41
                  E227K(8),2
                  E268G(7),44
                  E382D(3),47
                  E383D(2),46
                  E627K(1),50
                  E70K(8),43
                  F313Y(5),41
                  G16D(5),41
                  G266E(7),51
                  I178V(8),27
                  I322V(3),38
                  I539V(1),11
                  K270R(7),50
                  K312R(3),40
                  K54R(2),36
                  K702R(1),42
                  K716R(3),41
                  L136M(5),44
                  L234I(7),2
                  L283P(5),38
                  L475M(1),50
                  L576I(2),47
                  N375S(2),31
                  N473S(5),28
                  P28L(3),37
                  Q330K(7),38
                  Q357K(5),39
                  R100I(5),10
                  S272N(7),49
                  S297N(8),49
                  S400L(3),41
                  S654N(2),38
                  T108A(1),2
                  T121A(7),50
                  T552S(3),41
                  V100A(3),41
                  V105M(5),41
                  V114I(1),46
                  V33I(5),48
                  V473L(2),47
                  V645M(2),31


                  seasonal H1N1 from 2007 still had 31 of these 46 mutations from 1918,
                  ******=pan2009 has 10 of these 46 mutations:

                  N375S(2),E382D(3),V33I(5),V105M(5),Q357K(5),G266E( 7),K270R(7)
                  E70K(8),I178V(8),D209N(8)

                  N375S(2),E382D(3),G266E(7),K270R(7) are coincidence, since these
                  segments do not come from 1918
                  I'm interested in expert panflu damage estimates
                  my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

                  Comment


                  • #10
                    Re: List of Mutations

                    seasonal H1N1 from 2007 still had 31 of these 46 mutations from 1918,
                    ******=pan2009 has 10 of these 46 mutations:

                    N375S(2),E382D(3),V33I(5),V105M(5),Q357K(5),G266E( 7),K270R(7)
                    E70K(8),I178V(8),D209N(8)
                    That's amazing that those mutations survived for over 100 years (if I'm understanding correctly). Can we assume they are important ones for survival of the flu?

                    N375S(2),E382D(3),G266E(7),K270R(7) are coincidence, since these segments do not come from 1918
                    1918 had those mutations but they came from somewhere else? Where did they come from then?
                    The salvage of human life ought to be placed above barter and exchange ~ Louis Harris, 1918

                    Comment


                    • #11
                      Re: List of Mutations

                      some mutations will survive statistically.
                      31 from 46 is a lot, fewer in the classical swine-lineage (22 until 1977),
                      but the swine-viruses do not descend so directly from 1918-flu.

                      Some mutations were acquired by pan1918 and pan2009(tripl1998)
                      independently

                      new introductions into mammals had these distances from the bird-
                      index in the inner segments:

                      1918:8+7+10+9+7+5 human,North America
                      1957:-+5+-+-+-+- human,China
                      1968:-+4+-+-+-+- human,China
                      1979:8+5+14+5+3+9 swine,Europe
                      1998:12+-+10+-+-+- swine,USA
                      1963:8+12+14+15+1+10 equine,Miami
                      1956:54+45+42+30+36+69 equine,Prague
                      I'm interested in expert panflu damage estimates
                      my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

                      Comment


                      • #12
                        Re: List of Mutations

                        Do pan1957 and pan1968 also share any or all of the 10?
                        The salvage of human life ought to be placed above barter and exchange ~ Louis Harris, 1918

                        Comment


                        • #13
                          Re: List of Mutations

                          pan1957,segment 2:V114I(000100),E172I(000000),N375S(0,0,17,36,29,0 ),A401V(000100),R430K(0,0,0,14,2,0)
                          pan1968,segment 2:K121R(010000),L212V(000000),R327K(000200),N375S( 0,0,17,36,29,0)

                          in parentheses, how often that mutation occurs in my database
                          of 245 avian segment2s collected before 1985 in continents
                          (Africa:3,Asia:19,Europe:33,North-America:158,Ozeania:32,South-America:0)

                          N375S is in all 3 pans
                          I'm interested in expert panflu damage estimates
                          my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

                          Comment


                          • #14
                            Re: List of Mutations

                            Did we know this before?

                            Is it found commonly in seasonal H1, and H3, etc?
                            The salvage of human life ought to be placed above barter and exchange ~ Louis Harris, 1918

                            Comment


                            • #15
                              Re: List of Mutations

                              before the "invention" of the bird-index, we didn't know
                              that these were "mutations" , it could have been the standard

                              the equine(H3N8) virus from 1963 also had N375S, but not the European Swine(H1N1) from ~1978

                              sw78(2):N105T,I517V,R584H,A587T,N642S
                              eq63(2):G154D,A157S,D175N,K214R,R215K,S261R,N275S, E383D,R386K,K429R,R430K,N642S


                              I think 375S is still in seasonal H3N2 while H1N1 mutated back to 375N in the 40s or 50s
                              I'm interested in expert panflu damage estimates
                              my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

                              Comment

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