Strong dependence between ZIKV molecular rate estimates and host source of viral sequences


#21

The actual evolutionary rate is not actually that important or interesting. The actual value tells you nothing about adaptation - there are too many competing stocastic factors that effect it. Sure, it might be different in a human-mosquito-human cycle than a monkey-mosquito-monkey cycle (or whatever the sylvatic host is) but it doesn’t mean it has changed in nature or is adapting.

The rate is just useful to calibrate the tree to infer the timescale - and getting a good reliable timescale on this outbreak seems like an important goal right now. It is best to calibrate the tree as close to the nodes that you are interested in. To understand when and how it got into South America, what we need is a couple of hundred genomes from affected countries spread over the last five years. They need to be directly sequenced from samples.


#22

Completely agree that resequencing of older strains would be much better than trying to make back calculations from T/C rates. That’d require somebody having the original samples in a freezer though, as opposed to vials with already passaged strains. Hopefully it’ll be possible to get these - would certainly be very helpful!


#23

It would certainly be interesting from an ecological point of view, it doesn’t seem like high priority. Sequencing the shit out* of samples in Asia, Polynesia and the Americas both contemporary and going back 5-10 years for frozen samples is what is needed right now. That would produce a good estimate of the recent timescale and provide a strong framework for tracking forward.

  • A formal scientific expression derived from ‘The Martian’

#24

From these analyses and comments posted maybe we can conclude that African ZIKV sequences currently available, that were mainly retrieved from sylvatic transmissions, should not be used to calibrate/infer the timescale of recent human outbreaks because: 1) viral substitution rates in sylvatic and urban transmission cycles could be different, 2) most of the old African sequences were sequenced after multiple passages, 3) many recent African sequences could have problems of sequence integrity and/or recombination, or 4) a combination of all those factors previously described.

Because ZIKV outbreaks in South Pacific and the Americas seems to be of recent origin (2013-2015), older ZIKV sequences from urban epidemics (5-10 years ago) are probably only available in frozen samples from Asia and/or Western Pacific. Anyway, it could be also a good idea to performed retrospective studies of ZIKV infections in frozen acute febrile illness samples in the Americas taken before 2015 and that were negative for DENV and CHIKV. ZIKV may have been circulating for some time in the Americas, but remained undetected as ZIKV infections may have been attributed to other endemic arboviruses with similar clinical presentations.


#25

Good Morning - In the spirit of Eddie’s concerns about isolate integrity and to supplement what Kristian posted - this is my catalog of sequencing as of 29Feb16 (still updating) via my digging through Genbank and going back to the original publications. We’re prepping a manuscript and this will in supplemental in CSV format but I thought you might find it useful? You will some sequences repeated (genome, envelope). Some sequences were only E gene, some were both so you’ll see duplication of accessions, they are in order of accession. For passaging it’s host followed by a number that number is how many times. Ie. Ae_psuedoscutellaris_7 = Ae. psuedo 7 times - Cheers, Mel

Accession/Region/Isolate/Host_Vector/Location/Date/Note/Sequencing/Passage_History
AF372422/envelope/Spondweni/monkey/Uganda/1947/na/Sanger/unk
AY632535/envelope/MR766/Mac_mullatta/Uganda/1947/na/Sanger/suckling_mouse_1-3_from_CDC
AY632535/genome/MR766/Mac_mullatta/Uganda/1947/na/Sanger/suckling_mouse_1-3_from_CDC
EU545988/envelope/UNK/H_sapiens/Micronesia/2007-06/na/Sanger/unk
EU545988/genome/UNK/H_sapiens/Micronesia/2007-06/na/Sanger/unk
HQ234498/envelope/MR766/sentinel_rhesus/Uganda/1947/na/Sanger/suckling_mouse_146_Ae_albopictus_1
HQ234499/envelope/P6-740/Ae_aegypti/Malaysia/1966/na/Sanger/suckling_mouse_6_Vero_1_BHK_1_Ae_albopictus_1
HQ234499/genome/P6-740/Ae_aegypti/Malaysia/1966/na/Sanger/suckling_mouse_6_Vero_1_BHK_1_Ae_albopictus_1
HQ234500/envelope/IbH_30656/H_sapiens/Nigeria/1968/na/Sanger/suckling_mouse_21_Vero_1
HQ234500/genome/IbH_30656/H_sapiens/Nigeria/1968/na/Sanger/suckling_mouse_21_Vero_1
HQ234501/envelope/ArD_41519/Ae_africanus/Senegal/1984/recombination detected RDPv4/Sanger/AP61_Ae_psuedoscutellaris_1_C636_Ae_albopictus_2
HQ234501/genome/ArD_41519/Ae_africanus/Senegal/1984/recombination detected RDPv4/Sanger/AP61_Ae_psuedoscutellaris_1_C636_Ae_albopictus_2
JN860885/envelope/FSS13025/H_sapiens/Cambodia/2010/na/Sanger/Vero_1
JN860885/genome/FSS13025/H_sapiens/Cambodia/2010/na/Sanger/Vero_1
KF268948/envelope/ARB13565/Ae_africanus/CAR/1979/na/Illumina/suckling_mouse_3_Vero_E6_1
KF268948/genome/ARB13565/Ae_africanus/CAR/1979/na/Illumina/suckling_mouse_3_Vero_E6_1
KF268949/envelope/ARB15076/Ae_opok/CAR/1980/na/Illumina/suckling_mouse_3_Vero_E6_1
KF268949/genome/ARB15076/Ae_opok/CAR/1980/na/Illumina/suckling_mouse_3_Vero_E6_1
KF268950/envelope/ARB7701/Ae_africanus/CAR/1976/na/Illumina/suckling_mouse_3_Vero_E6_1
KF268950/genome/ARB7701/Ae_africanus/CAR/1976/na/Illumina/suckling_mouse_3_Vero_E6_1
KF270886/envelope/CCB870/H_sapiens/Gabon/2007/na/Sanger/Ae_psuedoscutellaris_7
KF383015/envelope/ArD149810/Ae_dalzieli/Senegal/2001/recombination detected by phylogenetic incongruency/Sanger/Ae_psuedoscutellaris_7
KF383016/envelope/ArD149917/Ae_dalzieli/Senegal/2001/recombination detected by phylogenetic incongruency/Sanger/Ae_psuedoscutellaris_7
KF383017/envelope/ArD149938/Ae_dalzieli/Senegal/2001/recombination detected by phylogenetic incongruency/Sanger/Ae_psuedoscutellaris_7
KF383018/envelope/ArD141170/Ae_dalzieli/Senegal/2001/recombination detected by phylogenetic incongruency/Sanger/Ae_psuedoscutellaris_7
KF383019/envelope/ArD132915/Ae_dalzieli/Senegal/1998/recombination detected by phylogenetic incongruency/Sanger/Ae_psuedoscutellaris_7
KF383020/envelope/ArA1465/Ae_africanus/Senegal/1998/recombination detected by phylogenetic incongruency Faye detected recombination/Sanger/Ae_psuedoscutellaris_7
KF383021/envelope/ArD132912/Ae_dalzieli/Senegal/1998/recombination detected by phylogenetic incongruency/Sanger/Ae_psuedoscutellaris_7
KF383022/envelope/ArD127988/Ae_furcifer/Senegal/1997/recombination detected RDPv4/Sanger/Ae_psuedoscutellaris_7
KF383023/envelope/ArD127987/Ae_luteocephalus/Senegal/1997/recombination detected RDPv4/Sanger/Ae_psuedoscutellaris_7
KF383024/envelope/ArD127984/Ae_furcifer/Senegal/1997/recombination detected RDPv4/Sanger/Ae_psuedoscutellaris_7
KF383025/envelope/ArD127707/Ae_furcifer/Senegal/1997/recombination detected RDPv4/Sanger/Ae_psuedoscutellaris_7
KF383026/envelope/ArD127994/Ae_taylori/Senegal/1997/recombination detected RDPv4/Sanger/Ae_psuedoscutellaris_7
KF383027/envelope/ArD127710/Ae_taylori/Senegal/1997/recombination detected RDPv4/Sanger/Ae_psuedoscutellaris_7
KF383028/envelope/ArD165531/Ae_dalzieli/Senegal/2002/recombination detected RDPv4/Sanger/Ae_psuedoscutellaris_7
KF383029/envelope/ArD165522/Ae_vittatus/Senegal/2002/recombination detected RDPv4/Sanger/Ae_psuedoscutellaris_7
KF383030/envelope/ArA2718/Ae_luteocephalus/BurkinaFaso/1981/recombination detected RDPv4/Sanger/Ae_psuedoscutellaris_7
KF383031/envelope/ArD9957/Ae_furcifer/Senegal/1969/recombination detected RDPv4/Sanger/Ae_psuedoscutellaris_7
KF383032/envelope/ArD30101/Ae_luteocephalus/Senegal/1979/apart of clade where recombinants were detected by RDPv4/Sanger/Ae_psuedoscutellaris_7
KF383033/envelope/ArD30332/Ce_aethiops/Senegal/1979/recombination detected RDPv4/Sanger/Ae_psuedoscutellaris_7
KF383034/envelope/ArD30156/Ae_furcifer/Senegal/1979/recombination detected RDPv4/Sanger/Ae_psuedoscutellaris_7
KF383035/envelope/MR1429/Mac_mullatta/Uganda/1963/na/Sanger/Ae_psuedoscutellaris_7
KF383036/envelope/ArA975/Ae_aegypti/CotedIvoire/1999/na/Sanger/Ae_psuedoscutellaris_7
KF383037/envelope/ArA506/Ae_vittatus/CotedIvoire/1996/na/Sanger/Ae_psuedoscutellaris_7
KF383038/envelope/ArA986/Ae_furcifer/CotedIvoire/1999/recombination detected RDPv4 Faye detected recombination/Sanger/Ae_psuedoscutellaris_7
KF383039/envelope/HD78788/H_sapiens/Senegal/1991/recombination detected RDPv4 Faye detected recombination/Sanger/Ae_psuedoscutellaris_7
KF383040/envelope/ArA27101/Ae_opok/CotedIvoire/1990/Faye detected recombination/Sanger/Ae_psuedoscutellaris_7
KF383041/envelope/ArA27290/Ae_opok/CotedIvoire/1990/Faye detected recombination/Sanger/Ae_psuedoscutellaris_7
KF383042/envelope/ArA27096/Ae_africanus/CotedIvoire/1990/recombination detected RDPv4 Faye detected recombination/Sanger/Ae_psuedoscutellaris_7
KF383043/envelope/ArA27443/Ae_grahamii/CotedIvoire/1990/Faye detected recombination/Sanger/Ae_psuedoscutellaris_7
KF383044/envelope/ArA27407/Ae_africanus/CotedIvoire/1990/Faye detected recombination/Sanger/Ae_psuedoscutellaris_7
KF383045/envelope/ArA27106/Ae_luteocephalus/CotedIvoire/1990/Faye detected recombination/Sanger/Ae_psuedoscutellaris_7
KF383046/envelope/ArA982/Ae_vittatus/CotedIvoire/1999/recombination detected RDPv4 Faye detected recombination/Sanger/Ae_psuedoscutellaris_7
KF383115/envelope/ArB1362/Ae_africanus/CAR/1968/na/Sanger/Ae_psuedoscutellaris_7
KF383115/genome/ArB1362/Ae_africanus/CAR/1968/na/Sanger/Ae_psuedoscutellaris_7
KF383116/envelope/ArD7117/Ae_luteocephalus/Senegal/1968/recombination detected RDPv4/Sanger/Ae_psuedoscutellaris_7
KF383116/genome/ArD7117/Ae_luteocephalus/Senegal/1968/recombination detected RDPv4/Sanger/Ae_psuedoscutellaris_7
KF383117/envelope/ArD128000/Ae_luteocephalus/Senegal/1997/recombination detected RDPv4 Faye detected recombination/Sanger/Ae_psuedoscutellaris_7
KF383117/genome/ArD128000/Ae_luteocephalus/Senegal/1997/recombination detected RDPv4 Faye detected recombination/Sanger/Ae_psuedoscutellaris_7
KF383118/envelope/ArD157995/Ae_dalzieli/Senegal/2001/recombination detected RDPv4/Sanger/Ae_psuedoscutellaris_7
KF383118/genome/ArD157995/Ae_dalzieli/Senegal/2001/recombination detected RDPv4/Sanger/Ae_psuedoscutellaris_7
KF383119/envelope/ArD158084/Ae_dalzieli/Senegal/2001/na/Sanger/Ae_psuedoscutellaris_7
KF383119/genome/ArD158084/Ae_dalzieli/Senegal/2001/na/Sanger/Ae_psuedoscutellaris_7
KF383120/envelope/ArD142623/An_coustani/Nigeria/2000/highly divergent Faye detected recombination/Sanger/Ae_psuedoscutellaris_7
KF993678/envelope/PLCalZV/H_sapiens/Canada/2013-02-19/na/Sanger/Vero_E6
KF993678/genome/PLCalZV/H_sapiens/Canada/2013-02-19/na/Sanger/Vero_E6
KJ634273/envelope/CKISL2014/H_sapiens/CookIslands/2014/na/IonTorrent/unk
KJ776791 /envelope/H/PF/2013/H_sapiens/FrenchPolynesia/2013-11-28/na/IonTorrent/Vero_3
KJ776791 /genome/H/PF/2013/H_sapiens/French Polynesia/2013-11-28/na/Sanger/Vero_3
KU312312 /envelope/Z1106033/H_sapiens/Suriname/2015-10-02/na/Sanger/unk
KU312312 /genome/Z1106033/H_sapiens/Suriname/2015-10-02/na/Sanger/unk
KU312313/envelope/Z1106032/H_sapiens/Suriname/2015/na/Sanger/unk
KU312314/envelope/Z1106031/H_sapiens/Suriname/2015/na/Sanger/unk
KU312315/envelope/Z1106027/H_sapiens/Suriname/2015/na/Sanger/unk
KU321639/envelope/ZikaSPH2015/H_sapiens/Brazil/2015/na/IonTorrent/unk
KU321639/genome/ZikaSPH2015/H_sapiens/Brazil/2015/na/IonTorrent/unk
KU365777/envelope/BeH818995/H_sapiens/Brazil/2015/na/IonTorrent_Roche454/unk
KU365777/genome/BeH818995/H_sapiens/Brazil/2015/na/IonTorrent_Roche454/unk
KU365778/envelope/BeH819015/H_sapiens/Brazil/2015/na/IonTorrent_Roche454/unk
KU365778/genome/BeH819015/H_sapiens/Brazil/2015/na/IonTorrent_Roche454/unk
KU365779/envelope/BeH819966/H_sapiens/Brazil/2015/na/IonTorrent_Roche454/unk
KU365779/genome/BeH819966/H_sapiens/Brazil/2015/na/IonTorrent_Roche454/unk
KU365780/envelope/BeH815744/H_sapiens/Brazil/2015/na/IonTorrent_Roche454/unk
KU365780/genome/BeH815744/H_sapiens/Brazil/2015/na/IonTorrent_Roche454/unk
KU497555/envelope/ZKV2015/H_sapiens/Brazil/2015-11-30/na/Illumina/unk
KU497555/genome/ZKV2015/H_sapiens/Brazil/2015-11-30/na/Illumina/unk
KU501215/envelope/PRVABC59/H_sapiens/PuertoRico/2015-12-01/na/IonTorrent/unk
KU501215/genome/PRVABC59/H_sapiens/PuertoRico/2015-12-01/na/IonTorrent/unk
KU501216/envelope/103344/H_sapiens/Guatemala/2015-12-01/na/IonTorrent/unk
KU501216/genome/103344/H_sapiens/Guatemala/2015-12-01/na/IonTorrent/unk
KU501217/envelope/8375/H_sapiens/Guatemala/2015-11-01/na/IonTorrent/unk
KU501217/genome/8375/H_sapiens/Guatemala/2015-11-01/na/IonTorrent/unk
KU509998/envelope/1225/H_sapiens/Haiti/2014-12-12/na/Sanger/unk
KU509998/genome/1225/H_sapiens/Haiti/2014-12-12/na/Sanger/unk
KU527068/envelope/Natal_RGN/H_sapiens/Brazil/2015/na/IonTorrent/unk
KU527068/genome/Natal_RGN/H_sapiens/Brazil/2015/na/IonTorrent/unk
KU646827/envelope/Si323/H_sapiens/Colombia/2015-11-10/na/Sanger/unk
KU646828/envelope/Si322/H_sapiens/Colombia/2015-11-10/na/Sanger/unk
KU647676/envelope/MRS_OPY_Martinique_PaRi/H_sapiens/Martinique/2015-12/na/IonTorrent/unk
KU647676/genome/MRS_OPY_Martinique_PaRi/H_sapiens/Martinique/2015-12/na/IonTorrent/unk
KU681081/envelope/SV0127-14/H_sapiens/Thailand/2014-07-19/na/Illumina/Tox_splendens_1_passage=C636_Ae_albopictus_1
KU681081/genome/SV0127-14/H_sapiens/Thailand/2014-07-19/na/Illumina/Tox_splendens_1_passage=C636_Ae_albopictus_1
KU681082/envelope/CPC-0740/H_sapiens/Philippines/2012-05-09/na/Illumina/Tox_splendens_1_passage=C636_Ae_albopictus_1
KU681082/genome/CPC-0740/H_sapiens/Philippines/2012-05-09/na/Illumina/Tox_splendens_1_passage=C636_Ae_albopictus_1
KU707826/envelope/SSABR1/H_sapiens/Brazil/2015-07-01/na/IonTorrent/unk
KU707826/genome/SSABR1/H_sapiens/Brazil/2015-07-01/na/IonTorrent/unk