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  • #16
    Re: low mutation rates in flu-viruses

    Originally posted by Vibrant62 View Post
    There is another theory that could explain the phenomenom.

    We know that viri held in deep freeze in artic and antarctic ice are still - sometimes - viable when released from deep freeze.

    It is entirely possible that birds or other vectors have transported viruses to areas where subzero temperatures predominate, and that, with global warming and ice melts such viruses are released again into the environment.

    Thus a virus from 1978 (or prior) could have become locked in ice, and then become released as warming has resulted in ice melts with a subsequent exposure to a viable host, restarting the cycle.

    To test such a theory, where exactly were viral samples that matched earlier (unchanged) samples identified? Was it in a cold temperature area? Could it explain what has been seen in genetic sequence samples?

    Just to add to the mix...
    Please provide reference for viable virus isolated from ice.

    Comment


    • #17
      Re: low mutation rates in flu-viruses

      minimum distance in 0/00 to groups :

      Code:
      19 times HK 1970s
      059,077,092,097,047,393,025,057,   37.Ck/Germany/n/1949(H10N7)     
      099,093,091,369,068,393,044,053,   38.fowl/Dobson/1927(H7N7)       
      064,080,055,088,034,392,026,031,   40.Dk/UKR/1/1963(H3N8)          
      040,081,071,082,040,071,031,025,   41.Ck/Scotland/1959(H5N1)       
      046,082,066,093,074,123,054,050,   42.human/China/GD02/06(H5N1)    
      042,076,079,090,074,114,058,051,   43.Bar-h Gs/Qinghai/62/05(H5N1) 
      138,160,133,348,126,133,082,097,   44.Sw/1931(H1N1)                
      134,151,129,343,114,129,068,059,   45.Brevig Mission/1/1918(H1N1)  
      143,162,136,342,130,164,093,087,   46.Alaska/1935(H1N1)            
      148,161,136,345,141,169,084,086,   47.Hickox/1940(H1N1)            
      166,175,148,351,154,199,112,115,   48.Kansas/UR06-0068/2007(H1N1)  
      150,074,144,081,146,069,093,087,   49.Japan/305/57(H2N2)           
      153,085,145,062,154,096,096,104,   50.Russia/WO0200884/72(H3N2)    
      158,117,158,148,169,149,111,124,   51.Texas/UR06-0356/2007(H3N2)   
      
      6 times Hubei 1997
      067,082,102,470,064,461,024,267,   37.Ck/Germany/n/1949(H10N7)     
      103,100,101,466,072,466,048,058,   38.fowl/Dobson/1927(H7N7)       
      064,084,066,473,061,397,024,035,   40.Dk/UKR/1/1963(H3N8)          
      065,087,086,120,055,114,030,030,   41.Ck/Scotland/1959(H5N1)       
      054,074,070,038,064,043,017,052,   42.human/China/GD02/06(H5N1)    
      049,065,061,037,065,019,015,051,   43.Bar-h Gs/Qinghai/62/05(H5N1) 
      140,159,138,350,130,154,082,096,   44.Sw/1931(H1N1)                
      135,151,133,349,119,168,066,060,   45.Brevig Mission/1/1918(H1N1)  
      147,162,140,362,134,187,093,091,   46.Alaska/1935(H1N1)            
      153,158,141,364,142,197,086,087,   47.Hickox/1940(H1N1)            
      170,175,152,370,153,213,115,117,   48.Kansas/UR06-0068/2007(H1N1)  
      154,081,148,301,148,495,095,092,   49.Japan/305/57(H2N2)           
      160,090,144,483,157,473,098,106,   50.Russia/WO0200884/72(H3N2)    
      162,122,160,490,170,482,114,124,   51.Texas/UR06-0356/2007(H3N2)   
      
      11 times Henan 2004
      071,082,107,476,065,488,029,269,   37.Ck/Germany/n/1949(H10N7)     
      105,103,102,466,074,491,052,053,   38.fowl/Dobson/1927(H7N7)       
      064,086,066,480,064,398,029,036,   40.Dk/UKR/1/1963(H3N8)          
      061,089,089,126,057,124,035,027,   41.Ck/Scotland/1959(H5N1)       
      021,022,061,025,009,033,007,018,   42.human/China/GD02/06(H5N1)    
      018,016,016,022,012,011,009,019,   43.Bar-h Gs/Qinghai/62/05(H5N1) 
      146,160,139,352,133,168,087,096,   44.Sw/1931(H1N1)                
      141,151,136,352,117,171,069,057,   45.Brevig Mission/1/1918(H1N1)  
      152,162,143,367,133,190,096,090,   46.Alaska/1935(H1N1)            
      157,162,139,363,140,199,089,085,   47.Hickox/1940(H1N1)            
      171,176,151,370,151,216,116,109,   48.Kansas/UR06-0068/2007(H1N1)  
      158,079,148,302,146,492,099,090,   49.Japan/305/57(H2N2)           
      161,092,146,485,159,481,103,112,   50.Russia/WO0200884/72(H3N2)    
      164,125,159,494,170,490,117,129,   51.Texas/UR06-0356/2007(H3N2)   
      
      032,011,016,080,013,120,013,014,   HK-Henan
      010,003,016,020,003,029,005,008,   Hubei-Henan
      034,011,017,072,014,095,008,012,   HK - Hubei
      I'm interested in expert panflu damage estimates
      my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

      Comment


      • #18
        Re: low mutation rates in flu-viruses

        a good example is also
        A/Guangxi/50/2005(H5N1) {gx50} which has only 49 differences
        in 3 years to A/Henan/16/2004.
        gx50 can be viewn as the best matching anchestor-virus to current
        H5N1 in most segments.

        These slow evolutions with few mutations are rare and not seen
        in human flu AFAIK with the exception of 1977 H1N1.
        In the Qinghai strain we have one (and only one) other such example :
        the Hungary-Suffolk virus. It suggests an abiotic reservoir,
        or some place inside the bodies, where the virus can survive for
        some time without mutating/replication.
        Could this be the key why the virus is so successful in
        SE-Asia ? What could be the reservoir where the virus
        survives without mutating ? Why is this obviously useful
        feature so rare in influenza ?
        I'm interested in expert panflu damage estimates
        my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

        Comment


        • #19
          Re: low mutation rates in flu-viruses

          strange low-mutation-rate in PB2:

          Code:
                                                     0000000000000000000000000000000000000000000011111111111111111111111111111111111111111111111111111111111111111112222222222222222
          PB2                                        0001222223333333444445555666677788888999999900001112222223333334444444555555555566666677777777777888888999999990000000000111222
                                                     4555557780001359047792289566612316788022348902494470247890112780566789113455678924445502234455667345678026778891233445799124128
                                                     6576250953695943271752887403671805925014621080153736455706176164514321251947924361246972810605149921081599176982814694948842866
          -codon-position----------------------------11                            1  1               1       1              11        1         1            1     2     2  1   1  
          ---Index-----------------------------------TCATGGATGTCAAGCTAACCTGTGAGGCCGTGTCCCCGTATGGACACACCTATATCAAGCACTGAGGGGTTGTCGCTCTGAGACGAGTCCACAGAGATTGTGGGTCCGCCCCCCATACCGCAGAGGG
          A/Dk/Hongkong/7/1975(H3N2)                 ...............................................................................................................................
          A/Dk/Nanchang/1681/1992(H3N8)              .......C.....A.CG.TGCA.AG....A..CT...A.G.......GTTCGAGC........A..A.A....A.......AG...A.T.GTG....C....AAC......T..GA..T....G...
          A/Dk/Zhejiang/11/00(H5N1)                  ....A.............T....A........C.T....G.A......T....GC.......C..AAA...A......C..A......T.GT......C..........T..TT.....A......A
          A/black Dk/Western AUS/4954/1983(H3N8)     ....AA..AA...AT.......CA.AATG.CA...TT.C.G.A...T.TT.....TGCA.GT..G..A..C.C.ATCT.A...AAG.C.T.T.AGA..C.......AAT.......GG.ATGA....
          A/slaty-backed gull/Shandong/38/04(H5N1)   CTGC..G.A.TGG....GT....A.A.TT..A.T......A..GTG..T..........A.T.......C..........G..........T..G.G..ACA.A.T....T.....G.....A.AA.
          omitting polymorphisms which only occur once:

          Code:
                                                     0000000000111111111111222
                                                     2234667889122344677789001
                                                     5837563162447767424640492
                                                     2591438054755143180125944
          -codon-position----------------------------        1 1              
          Index--------------------------------------GGGCGCGTCACATCGGGCAATGAGG
          A/Dk/HK/7/1975(H3N2)                       .........................
          A/Dk/Nanchang/1681/1992(H3N8)              ..AT...CTGTGC.A.ATG..A...
          A/Dk/Zhejiang/11/00(H5N1)                  A..T...C.G.GC.AAATG.C..A.
          A/black Dk/Western AUS/4954/1983(H3N8)     AAA.ATA...T..T.A...GC.GAA
          A/slaty-backed gull/Shandong/38/04(H5N1)   .A.TATA.T....T.....G.AG.A

          Code:
          #differences in PB2                        1   2   3   4   5   6   7 
          ---------------------------------------------------------------------
            1 >A/Dk/HK/7/1975(H3N2)                  0, 43, 56, 94, 39, 98, 26
            2 >A/Dk/Nanchang/1681/92(H3N8)          43,  0, 89,115, 70,119, 45
            3 >A/black Dk/W.AUS/4954/83(H3N8)       56, 89,  0,111, 71,132, 68
            4 >A/Ck/Scotland/1959(H5N1)             94,115,111,  0,113,168,108
            5 >A/slaty-backed gull/SD/38/04(H5N1)   39, 70, 71,113,  0,125, 57
            6 >A/Bar-h Gs/Qinghai/62/05(H5N1)       98,119,132,168,125,  0, 78
            7 >A/Dk/Zhejiang/11/00(H5N1)            26, 45, 68,108, 57, 78,  0
          the 168 differences in PB2 between the Qinghai virus and the 1959-virus
          is already so low, that Qinghai might be a direct descendant of 1959.
          But some of the other differences are even much lower, so that
          we should assume either errors or slow evolution, which is unusual.
          The HK/75 virus had already given some examples of slow evolution
          above in this thread

          But it's not just this one virus. Close to HK75 in PB2 are e.g.
          A/Dk/HK/24/76(H4N2)
          A/Dk/HK/562/79(H10N9)
          A/Dk/HK/312/78(H5N3)

          A/Dk/Nanchang/1681/92(H3N8)
          A/black Dk/AUS/751/78(H3N8)
          I'm interested in expert panflu damage estimates
          my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

          Comment


          • #20
            Re: low mutation rates in flu-viruses

            compare the differences in PB2 between these 4 viruses:


            Code:
            #differences                         1   2   3   4 
            ---------------------------------------------------
              1 >A/duck/England/1956(H11N6)      0  85 103 127 
              2 >A/Dk/HK/7/1975(H3N2)           85   0  26  56 
              3 >A/Dk/Zhejiang/11/00(H5N1)     103  26   0  34 
              4 >A/Dk/Guangxi/35/01(H5N1)      127  56  34   0

            they are pretty much "in a line". No room for a lab-error,
            the "error" can't know the required mutations.

            This would all be not so surprising , if the date-differences
            would match the mutations-differences But :
            there are 25 years between 2) and 3), with
            only 26 differences !!
            I'm interested in expert panflu damage estimates
            my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

            Comment


            • #21
              Re: low mutation rates in flu-viruses

              now it seems that we can observe the same phenomenon
              in North America. More and more sequences are being uploaded
              and virus-segments with few differences but decades apart
              appear.
              I have not yet made a systematic list as above for
              HK-Hubei-Henan but e.g.
              A/pintail/Alaska/779/2005(H3N8)
              seems to have some low-distance relatives from the 70s
              or 80s in all segments.
              While at the same time being close to other viruses from 2005.

              segment 1 : 97.4% similarity for 14 years
              segment 2 : 97.5% similarity for 12 years
              segment 3 : 95.9% similarity for 26 years
              segment 4 : 97.1% similarity for 27 years
              segment 5 : 96.6% similarity for 24 years
              segment 6 : 96.3% similarity for 28 years
              segment 7 : 98.3% similarity for 27 years
              segment 8 : 97.4% similarity for 26 years

              these are different viruses for the segments, there
              was apparantly much reassortment.

              ---------edit1----------
              comparing 52 North American avian viruses from the 70s with
              248 North American avian viruses from 2000 or later

              Code:
              1978-2005: 39,29,40,28,28,32,16,15
              compare with Asia from post #1:
              Code:
              1977-2004: 29,11,17,81,13,99,14,19
              minimum:
              Code:
              27 years: 29,11,17,28,13,32,14,15
              (nucleotide-difference in 0/00)

              This low-mutation evolution isn't seen in human influenza
              and seems to be independent and rarer than "normal"
              evolution in birds. But it contributes significantly,
              so is the current H5N1 a result of this low mutation evolution
              in most segments since the 70s as shown above.

              What could it be ? And why isn't it in human flu ?
              (but some examples for swine too !)


              some possible explanations:

              * the virus could persist most of the time in the environment (water ?)
              and only some of the time actively replicating in birds
              * the virus could persist in some special organs/places inside
              some special species of birds (or other animals ?)
              * the virus has a method to replicate more reliably with fewer
              mutation-rates in some species under certain circumstances
              (as seen with influenza-B in humans)
              * some gene-configurations are particularly stable and although
              the mutation rate isn't lower, only few of them survive due
              to selection (including selection for synonymous mutations)



              I wish more bird-sequences from the 1970s from EurAsia
              I'm interested in expert panflu damage estimates
              my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

              Comment


              • #22
                Re: low mutation rates in flu-viruses

                I want to add this for the evolution of the Alaska avian viruses
                filename: swav18m.l6g

                Code:
                 18 >A/pintail/Alaska/779/2005(H3N8)            2314 2285 2203 1731 1530 1425  977  851   
                  4:144,109, 99,447, 92,425, 69,273   A/fowl/Rostock/45/1934(H7N1)               2341 2341 2233 1741 1565 1393 1027  890
                  5:141, 87, 90,494, 91,436, 64,276   A/Ck/Scotland/1959(H5N1)                   2341 2341 2233 1767 1565 1458 1027  890
                  6:152,115, 91,498,116,434, 86,278   A/Bar-h Gs/Qinghai/62/05(H5N1)             2287 2298 2185 1698 1493 1361  982  831
                  7:144,106, 73,489, 88,503, 65,282   A/tern/South Africa/1961(H5N3)             2341 2341 2233 1779 1565 1454 1027  890
                  8:142,105, 61,491, 96,500, 57,275   A/duck/Germany/1215/1973(H2N3)             2341 2341 2233 1773 1565 1410 1027  890
                  9:139, 96, 97,445, 95,483, 61,284   A/turkey/England/1963(H7N3)                2341 2341 2233 1738 1565 1369 1027  890
                 10: 65, 89,115,435, 75,507, 36, 35   A/turkey/Oregon/1971(H7N3)                 2280 2280 2151 1691 1540 1419 1002  855
                 11: 90,154,111,489, 64,504, 40, 50   A/duck/Memphis/546/1974(H11N9)             2341 2341  493 1760 1565 1460 1027  890
                 12:142, 88, 78,493, 94,471, 75,281   A/duck/England/1956(H11N6)                 2341 2341 2233 1760 1565 1464 1027  890
                 13:142, 86, 90,380, 90,481, 72,275   A/duck/Czechoslovakia/1956(H4N6)           2341 2341 2233 1738 1565 1426 1027  890
                 14:140, 90,104,449, 86,516, 62,100   A/Ck/Germany/n/1949(H10N7)                 2341 2343 2233 1728 1565 1464 1027  890
                 15:139, 94,105,451, 97,225, 78,281   A/quail/Italy/1117/1965(H10N8)             2341 2341 2233 1728 1565 1460 1027  890
                 16:147, 83, 74,147, 93,216, 60,280   A/Dk/UKR/1/1963(H3N8)                      2341 2341 2233 1764 1565 1461 1027  890
                 17:142,103, 65,152, 90,220, 65, 96   A/duck/Chabarovsk/1610/1972(H3N8)          2341 2341 2233 1765 1565 1460 1027  890
                 19:104,163,141,213,138,218, 58,289   A/equine/New York/1/1983(H3N8)             2299 2302 2192 1723 1519 1425  992  850
                 21:114,163,147,225,150,230, 64,289   A/swine/Chibi/01/2005/12/15(H3N8)          2341 2341 2233 1762 1565 1460 1027  889
                 22:164,132,125,202,119,485, 88,283   A/swine/Hong Kong/5190/99(H3N2)            1285 1292 1535 1595 1459 1380  964  838
                 23:155,125,164,206,172,487,103,274   A/Texas/UR06-0356/2007(H3N2)               2303 2297 2187 1701 1521 1428  988  848
                 24:149, 88,153,161,157,488, 89,281   A/Russia/WO0200884/72(H3N2)                2341 2341 2233 1765 1565 1466 1027  890
                 26:144, 83,151,483,145,486, 77,285   A/Index/1957(H2N2)                         2314 2317 2209 1730 1520 1447 1002  864
                 29:140,164,147,484,151,426, 74,279   A/Index/1977(H1N1)                         2298 2300 2194 1731 1506 1426 1002  848
                 34:148,175,157,495,156,431,103,287   A/Kansas/UR06-0068/2007(H1N1)              2283 2303 2197 1741 1506 1423  982  849
                 36:119,153,141,477,122,420, 57,278   A/Index/early human/1935(H1N1)             2280 2274 2151 1701 1497 1410  982  838
                 37:114,149,141,477,112,422, 51,275   A/Brevig Mission/1/1918(H1N1)              2280 2274 2151 1701 1497 1410  982  838
                 38:127,158,140,484,120,422, 64,282   A/Sw/Index/early swine/1935(H1N1)          2280 2274 2151 1701 1497 1410  982  838
                 43:139,167,161,480,152,431, 79,288   A/swine/Wisconsin/1/1957(H1N1)             2292 2298 2181 1730 1532 1418  995  855
                 55: 87,122, 49,511,164,423, 85,294   A/Wisconsin/10/98(H1N1)                    1600 2341 1494 1064 1512 1458 1027  890
                 57: 96,131, 66,467,164,429, 89,291   A/******/index/2009-02-01(H1N1)            2280 2274 2151 1701 1497 1410  982  863
                 64: 87,128, 59,465,161,482, 95,295   A/Swine/Hong Kong/915/2004/10/14(H1N2)     2276 2266 2151 1701 1515 1428  984  861
                 65: 97,125, 41,468,163,483, 72,293   A/Turkey/MO/24093/99(H1N2)                  787  706  729 1701  980 1434  360  846
                 68: 78,123, 51,201,175,480, 80,291   A/Swine/Nebraska/209/1998(H3N2)            2335 2275 2151 1702 1565 1410  996  847
                 69: 80,122, 46,200,163,481, 82,293   A/Sw/Index/triple-reassortant/1998(H3N2)   2341 2301 2202 1725 1565 1430 1012  870
                 71: 81,123, 48,199,163,483, 80,293   A/mallard/SD/Sg-00125/2007/09/19(H3N2)     2334 2335 2226 1763 1557 1444 1017  880
                 73: 66, 77, 68,479, 57,424, 33, 39   A/turkey/MO/21939/1987(H1N1)               2316 2294 2165 1748 1539 1418 1002  865
                 74: 60, 56, 83,472, 58,426, 42, 33   A/swine/Saskatchewan/18789/02(H1N1)        2280 2274 2151 1701 1497 1410  982  838
                 76:---,---,---,478,---,431,---,---   A/Anas crecca/Spain/1384/2007(H1N1)           3    3    3 1701    3 1410    3    3
                 78:149,109, 79,480,100,430, 61,100   A/duck/Italy/69238/2007(H1N1)              2308 2308 2200 1743 1530 1422  989  887
                 81:148,103,110,472, 96,432, 65,284   A/swine/Germany/2/1981(H1N1)=1578          2314 2313 2233 1778 1565 1412 1002  864
                 89:163,129,134,468,119,439,106,311   A/Thailand/271/2005(H1N1)                  2301 2193 2120 1778 1541 1452  994  846
                 90:141, 97, 50,481, 90,349, 69,280   A/shearwater/Australia/1/1973(H6N5)        2341 2341 2233 1744 1564 1454 1027  890
                 91:142,114, 69,477,103,442, 62, 96   A/duck/Taiwan/0526/72(H6N1)                2341 2340 2233 1744 1563 1458 1027  890
                 93: 93, 77,134,486, 69,483, 36, 36   A/Turkey/California/189/66(H9N2)           2257 2247 2140 1661 1505 1386  974  831
                 94: 69, 72,132,486, 71,478, 38,280   A/turkey/Wisconsin/1/1966(H9N2)            2341 2341 2233 1742 1565 1467 1027  890
                 95: 98,156,129,493, 69,435, 33,279   A/turkey/Ontario/6118/1968(H8N4)           2341 2341 2233 1744 1565 1462 1027  890
                I'm interested in expert panflu damage estimates
                my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

                Comment


                • #23
                  Re: low mutation rates in flu-viruses

                  Question - we know influenza virus can remain viable for an indefinite time in ice, and we are in a period of global warming and ice melts. Is it possible that viral reservoirs are being freed from ice during melts at the same time as possible hosts are around for wider dissemination, re-introducing older viral forms back into the mix?

                  Comment


                  • #24
                    Re: low mutation rates in flu-viruses

                    we have no evidence for this. flu has never been isolated from ice
                    in nature, AFAIK.
                    When you say: "indefinite time" then there should also be older
                    viruses around, 100 years or such, but that has never happened before,
                    AFAIK.
                    Also the samples from 1918 in permafrost were only small fragments,
                    hard to reconstruct. And they had to search a lot until they found
                    a body with some fragments.

                    maybe frozen droppings or frozen eggs or frozen bird-cadavers ?
                    Maybe some birds find and eat these frozen eggs, cadavers.

                    OK for Alaska, but in Hong Kong ??


                    We have a lot new bird sequences from USA and Alaska recently
                    shovelers,pintails,mallards, sandpiper

                    maybe I can make a more complete analysis when ******
                    stays calm


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

                    Last edited by gsgs; October 1, 2009, 04:46 AM. Reason: Alaska link
                    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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