392 research outputs found
From Molecular Genetics to Phylodynamics: Evolutionary Relevance of Mutation Rates Across Viruses
- Author
- A Drummond
- A Rector
- AJ Drummond
- AS Perelson
- Barbara Sherry
- BT Grenfell
- C Firth
- CL Althaus
- E Domingo
- E Nobusawa
- EC Holmes
- EC Holmes
- EC Holmes
- GM Jenkins
- HA Orr
- JJ Bull
- JK Pfeiffer
- JM Cuevas
- JM Malpica
- JP Anderson
- JW Drake
- K Hanada
- KM Pepin
- L Bromham
- LA Frederico
- M Kimura
- M Lynch
- M Salemi
- M Vignuzzi
- M Vignuzzi
- MP Davenport
- OG Pybus
- OG Pybus
- P Carrasco
- P Domingo-Calap
- R Sanjuán
- R Sanjuán
- Rafael Sanjuán
- S Duffy
- SY Ho
- WM Switzer
- Publication venue
- Public Library of Science
- Publication date
- 01/01/2012
- Field of study
Although evolution is a multifactorial process, theory posits that the speed of molecular evolution should be directly determined by the rate at which spontaneous mutations appear. To what extent these two biochemical and population-scale processes are related in nature, however, is largely unknown. Viruses are an ideal system for addressing this question because their evolution is fast enough to be observed in real time, and experimentally-determined mutation rates are abundant. This article provides statistically supported evidence that the mutation rate determines molecular evolution across all types of viruses. Properties of the viral genome such as its size and chemical composition are identified as major determinants of these rates. Furthermore, a quantitative analysis reveals that, as expected, evolution rates increase linearly with mutation rates for slowly mutating viruses. However, this relationship plateaus for fast mutating viruses. A model is proposed in which deleterious mutations impose an evolutionary speed limit and set an extinction threshold in nature. The model is consistent with data from replication kinetics, selection strength and chemical mutagenesis studies
Phylodynamic assessment of intervention strategies for the West African Ebola virus outbreak
- Author
- A Arias
- A Gelman
- A Pandey
- AJ Drummond
- AJ Drummond
- AJ Kucharski
- AM Kramer
- C Poletto
- DG Streicker
- DJ Park
- DL Ayres
- E Simon-Loriere
- EC Holmes
- F Bielejec
- G Dudas
- J Gardy
- J Quick
- J Wishart
- JA Backer
- JC Blackwood
- JR Kugelman
- JT Ladner
- K Modjarrad
- K Zinszer
- LQ Fang
- M Gill
- M Hasegawa
- MAR Ferreira
- MS Gill
- MSY Lau
- MSY Lau
- MW Carroll
- NR Faria
- NS Trovo
- OG Pybus
- OG Pybus
- P Lemey
- P Lemey
- P Nouvellet
- RE Kass
- S Baize
- S Dellicour
- S Dellicour
- S Dellicour
- SK Gire
- TD Hollingsworth
- The Global Consortium for H5N8 and Related Influenza Viruses.
- VM Minin
- VM Minin
- WHO Ebola Response Team.
- XL Meng
- Z Yang
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2018
- Field of study
Genetic analyses have provided important insights into Ebola virus spread during the recent West African outbreak, but their implications for specific intervention scenarios remain unclear. Here, we address this issue using a collection of phylodynamic approaches. We show that long-distance dispersal events were not crucial for epidemic expansion and that preventing viral lineage movement to any given administrative area would, in most cases, have had little impact. However, major urban areas were critical in attracting and disseminating the virus: preventing viral lineage movement to all three capitals simultaneously would have contained epidemic size to one-third. We also show that announcements of border closures were followed by a significant but transient effect on international virus dispersal. By quantifying the hypothetical impact of different intervention strategies, as well as the impact of barriers on dispersal frequency, our study illustrates how phylodynamic analyses can help to address specific epidemiological and outbreak control questions.info:eu-repo/semantics/publishe
Explaining the geographic spread of emerging epidemics: a framework for comparing viral phylogenies and environmental landscape data
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector
- Author
- Aad G
- Abajyan T
- Abbott B
- Abdallah J
- Abdinov O
- Aben R
- Abi B
- Abolins M
- AbouZeid OS
- Abramowicz H
- Abreu H
- Abulaitia Y
- Acharya BS
- Adamczyk L
- Adams DL
- Addy TN
- Adelman J
- Adomeit S
- Adye T
- Agatonovic-Jovin T
- Aguilar-Saavedra JA
- Agustoni M
- Ahlen SP
- Ahmadov F
- Aielli G
- Akesson TP
- Akimoto G
- Akimov AV
- Albert J
- Albrand S
- Alconada Verzini MJ
- Aleksa M
- Aleksandrov IN
- Alexa C
- Alexander G
- Alexandre G
- Alexopoulos T
- Alhroob M
- Alimonti G
- Alio L
- Alison J
- Allbrooke BMM
- Allison LJ
- Allport PP
- Allwood-Spiers SE
- Almond J
- Aloisio A
- Alon R
- Alonso A
- Alonso F
- Alpigiani C
- Altheimer A
- Alviggi MG
- Amako K
- Amelung C
- Ammosov VV
- Amor Dos Santos SP
- Amorim A
- Amoroso S
- Amram N
- Amundsen G
- Anastopoulos C
- Ancu LS
- Andari N
- Andeen T
- Anders CF
- Anders G
- Anderson KJ
- Andreazza A
- Andrei V
- Anduaga XS
- Angelidakis S
- Anger P
- Angerami A
- Anghinolfi F
- Anh TV
- Anisenkov AV
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- Antonaki A
- Antonelli M
- Antonov A
- Antos J
- Anulli F
- Aoki M
- Apolle R
- Arabidze G
- Aracena I
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- Arce ATH
- Arguin J-F
- Argyropoulos S
- Arik E
- Arik M
- Armbruster AJ
- Arnaez O
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- Artamonov A
- Artoni G
- Asai S
- Asbah N
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- Asman B
- Asquith L
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- Atlay NB
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- Zhemchugov A
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- Zurzolo G
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- Publication venue
- 'IOP Publishing'
- Publication date
- 01/01/2014
- Field of study
This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}andcorrespondtoanintegratedluminosityof4.6\;{\rm f}{{{\rm b}}^{-1}}.ThemeasurementisperformedbyreconstructingtheboostedWorZbosonsinsinglejets.ThereconstructedjetmassisusedtoidentifytheWandZbosons,andajetsubstructuremethodbasedonenergyclusterinformationinthejetcentre−of−massframeisusedtosuppressthelargemulti−jetbackground.Thecross−sectionforeventswithahadronicallydecayingWorZboson,withtransversemomentum{{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}andpseudorapidity|\eta |\lt 1.9,ismeasuredtobe{{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques
Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector
- Author
- Aad G
- Abbott B
- Abdallah J
- Abdelalim AA
- Abdesselam A
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- Zwalinski L
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 31/12/2010
- Field of study
The inclusive and dijet production cross-sections have been measured for jets
containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass
energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The
measurements use data corresponding to an integrated luminosity of 34 pb^-1.
The b-jets are identified using either a lifetime-based method, where secondary
decay vertices of b-hadrons in jets are reconstructed using information from
the tracking detectors, or a muon-based method where the presence of a muon is
used to identify semileptonic decays of b-hadrons inside jets. The inclusive
b-jet cross-section is measured as a function of transverse momentum in the
range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet
cross-section is measured as a function of the dijet invariant mass in the
range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets
and the angular variable chi in two dijet mass regions. The results are
compared with next-to-leading-order QCD predictions. Good agreement is observed
between the measured cross-sections and the predictions obtained using POWHEG +
Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet
cross-section. However, it does not reproduce the measured inclusive
cross-section well, particularly for central b-jets with large transverse
momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final
version published in European Physical Journal
Performance of the CMS Cathode Strip Chambers with Cosmic Rays
- Author
- Abadjiev K
- Abbaneo D
- Abbiendi G
- Abbrescia M
- Abdullin S
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- Altsybeev I
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- Publication venue
- 'IOP Publishing'
- Publication date
- 01/01/2009
- Field of study
The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device
in the CMS endcaps. Their performance has been evaluated using data taken
during a cosmic ray run in fall 2008. Measured noise levels are low, with the
number of noisy channels well below 1%. Coordinate resolution was measured for
all types of chambers, and fall in the range 47 microns to 243 microns. The
efficiencies for local charged track triggers, for hit and for segments
reconstruction were measured, and are above 99%. The timing resolution per
layer is approximately 5 ns
Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector
- Author
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- Zanzi D
- Zeitnitz C
- Zeman M
- Zemla A
- Zengel K
- Zenin O
- Zenis T
- Zerwas D
- Zhang D
- Zhang F
- Zhang H
- Zhang J
- Zhang L
- Zhang X
- Zhang Z
- Zhao Z
- Zhemchugov A
- Zhong J
- Zhou B
- Zhou L
- Zhou N
- Zhu CG
- Zhu H
- Zhu J
- Zhu Y
- Zhuang X
- Zhukov K
- Zibell A
- Zieminska D
- Zimine NI
- Zimmermann C
- Zimmermann R
- Zimmermann S
- Zimmermann S
- Zinonos Z
- Ziolkowski M
- Zobernig G
- Zoccoli A
- zur Nedden M
- Zurzolo G
- Zutshi V
- Zwalinski L
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2014
- Field of study
The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV
Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV
- Author
- Aad G
- Abbott B
- Abdallah J
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- Aben R
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- Smizanska M
- Smolek K
- Snesarev AA
- Snidero G
- Snyder S
- Sobie R
- Socher F
- Soffer A
- Soh DA
- Solans CA
- Solar M
- Solc J
- Soldatov EY
- Soldevila U
- Solodkov AA
- Soloshenko A
- Solovyanov OV
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- Sommer P
- Song HY
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- Stanek RW
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- Stanitzki MM
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- Strandberg J
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- Sulin VV
- Sultansoy S
- Sumida T
- Sun S
- Sun X
- Sundermann JE
- Suruliz K
- Susinno G
- Sutton MR
- Suzuki Y
- Svatos M
- Swedish S
- Swiatlowski M
- Sykora I
- Sykora T
- Ta D
- Taccini C
- Tackmann K
- Taenzer J
- Taffard A
- Tafirout R
- Taiblum N
- Takai H
- Takashima R
- Takeda H
- Takeshita T
- Takubo Y
- Talby M
- Talyshev AA
- Tam JYC
- Tan KG
- Tanaka J
- Tanaka R
- Tanaka S
- Tanaka S
- Tanasijczuk AJ
- Tannenwald BB
- Tannoury N
- Tapprogge S
- Tarem S
- Tarrade F
- Tartarelli GF
- Tas P
- Tasevsky M
- Tashiro T
- Tassi E
- Tayalati Y
- Taylor FE
- Taylor GN
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- Tehrani FS
- Teischinger FA
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- Temming KK
- Ten Kate H
- Teng PK
- Teoh JJ
- Terada S
- Terashi K
- Terron J
- Terzo S
- Testa M
- Teuscher RJ
- Therhaag J
- Theveneaux-Pelzer T
- Thomas JP
- Thomas-Wilsker J
- Thompson AS
- Thompson EN
- Thompson PD
- Thompson PD
- Thompson RJ
- Thomsen LA
- Thomson E
- Thomson M
- Thong WM
- Thun RP
- Tian F
- Tibbetts MJ
- Tikhomirov VO
- Tikhonov YA
- Timoshenko S
- Tiouchichine E
- Tipton P
- Tisserant S
- Todorov T
- Todorova-Nova S
- Toggerson B
- Tojo J
- Tokar S
- Tokushuku K
- Tollefson K
- Tolley E
- Tomlinson L
- Tomoto M
- Tompkins L
- Toms K
- Topilin ND
- Toro RC
- Torregrosa EF
- Torrence E
- Torres H
- Torro Pastor E
- Toth J
- Touchard F
- Tovey DR
- Tran HL
- Trefzger T
- Tremblet L
- Tricoli A
- Trigger IM
- Trincaz-Duvoid S
- Tripiana MF
- Trischuk W
- Trocme B
- Troncon C
- Trottier-McDonald M
- Trovatelli M
- True P
- Trzebinski M
- Trzupek A
- Tsarouchas C
- Tseng JC-L
- Tsiareshka PV
- Tsionou D
- Tsipolitis G
- Tsirintanis N
- Tsiskaridze S
- Tsiskaridze V
- Tskhadadze EG
- Tsukerman I
- Tsulaia V
- Tsuno S
- Tsybychev D
- Tudorache A
- Tudorache V
- Tuna AN
- Tupputi SA
- Turchikhin S
- Turecek D
- Turra R
- Tuts PM
- Tykhonov A
- Tylmad M
- Tyndel M
- Uchida K
- Ueda I
- Ueno R
- Ughetto M
- Ugland M
- Uhlenbrock M
- Ukegawa F
- Unal G
- Undrus A
- Unel G
- Ungaro FC
- Unno Y
- Unverdorben C
- Urbaniec D
- Urquijo P
- Usai G
- Usanova A
- Vacavant L
- Vacek V
- Vachon B
- Valencic N
- Valentinetti S
- Valero A
- Valery L
- Valkar S
- Vallecorsa S
- Van Den Wollenberg W
- Van Der Deijl PC
- van der Geer R
- van der Graaf H
- Van Der Leeuw R
- van der Ster D
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- Van Gemmeren P
- van Huysduynen LH
- Van Nieuwkoop J
- van Vulpen I
- Van Woerden MC
- Vanadia M
- Vandelli W
- Vanguri R
- Vaniachine A
- Vankov P
- Vannucci F
- Vaque FV
- Vardanyan G
- Vari R
- Varnes EW
- Varol T
- Varouchas D
- Vartapetian A
- Varvell KE
- Vazeille F
- Vazquez JGP
- Veatch J
- Veloso F
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- Veneziano S
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- Vercesi V
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- Vermeulen JC
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- Vichou I
- Vickey T
- Viehhauser GHA
- Viel S
- Vigne R
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- Vilucchi E
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- Virzi J
- Vivarelli I
- Vlachos S
- Vladoiu D
- Vlasak M
- Vogel A
- Vokac P
- Volpi G
- Volpi M
- von der Schmitt H
- von Radziewski H
- von Toerne E
- Vorobel V
- Vorobev K
- Vos M
- Voss R
- Vossebeld JH
- Vranjes N
- Vrba V
- Vreeswijk M
- Vuanh T
- Vuillermet R
- Vukotic I
- Vykydal Z
- Wagner P
- Wagner W
- Wahlberg H
- Wahrmund S
- Wakabayashi J
- Walder J
- Walker R
- Walkowiak W
- Wall R
- Waller P
- Walls FMG
- Walsh B
- Wang C
- Wang C
- Wang F
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- Wang H
- Wang J
- Wang J
- Wang K
- Wang R
- Wang SM
- Wang T
- Wang X
- Wanotayaroj C
- Warburton A
- Ward CP
- Wardrope DR
- Warsinsky M
- Washbrook A
- Wasicki C
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- Watson AT
- Watson IJ
- Watson MF
- Watts G
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- Weber MS
- Weber SW
- Webster JS
- Weidberg AR
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- Weinert B
- Weingarten J
- Weiser C
- Weits H
- Wells PS
- Wemans ADV
- Wenaus T
- Wendland D
- Weng Z
- Wengler T
- Wenig S
- Wermes N
- Werner M
- Werner P
- Wessels M
- Wetter J
- Whalen K
- White A
- White MJ
- White R
- White S
- Whiteson D
- Wicke D
- Wickens FJ
- Wiedenmann W
- Wielers M
- Wienemann P
- Wiglesworth C
- Wiik-Fuchs LAM
- Wijeratne PA
- Wildauer A
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- Wilkens HG
- Will JZ
- Williams HH
- Williams S
- Willis C
- Willocq S
- Wilson A
- Wilson JA
- Wingerter-Seez I
- Winklmeier F
- Winter BT
- Wittgen M
- Wittig T
- Wittkowski J
- Wollstadt SJ
- Wolter MW
- Wolters H
- Wong KHY
- Wosiek BK
- Wotschack J
- Woudstra MJ
- Wozniak KW
- Wright M
- Wu M
- Wu SL
- Wu X
- Wu Y
- Wulf E
- Wyatt TR
- Wynne BM
- Xella S
- Xiao M
- Xu D
- Xu L
- Yabsley B
- Yacoob S
- Yakabe R
- Yamada M
- Yamaguchi H
- Yamaguchi Y
- Yamamoto A
- Yamamoto K
- Yamamoto S
- Yamamura T
- Yamanaka T
- Yamauchi K
- Yamazaki Y
- Yan Z
- Yang H
- Yang H
- Yang UK
- Yang Y
- Yanush S
- Yao L
- Yao W-M
- Yasu Y
- Yatsenko E
- Ye J
- Ye S
- Yeletskikh I
- Yen AL
- Yildirim E
- Yildiz HD
- Yilmaz M
- Yoosoofmiya R
- Yorita K
- Yoshida R
- Yoshihara K
- Young C
- Young CJS
- Youssef S
- Yu DR
- Yu J
- Yu J
- Yu JM
- Yuan L
- Yurkewicz A
- Yusuff I
- Zabinski B
- Zaidan R
- Zaitsev AM
- Zaman A
- Zambito S
- Zanello L
- Zanzi D
- Zeitnitz C
- Zeman M
- Zemla A
- Zengel K
- Zenin O
- Zenis T
- Zerwas D
- Zhang D
- Zhang F
- Zhang H
- Zhang J
- Zhang L
- Zhang X
- Zhang Z
- Zhao Z
- Zhemchugov A
- Zhong J
- Zhou B
- Zhou L
- Zhou N
- Zhu CG
- Zhu H
- Zhu J
- Zhu Y
- Zhuang X
- Zhukov K
- Zibell A
- Zieminska D
- Zimine NI
- Zimmermann C
- Zimmermann R
- Zimmermann S
- Zimmermann S
- Zinonos Z
- Ziolkowski M
- Zobernig G
- Zoccoli A
- zur Nedden M
- Zurzolo G
- Zutshi V
- Zwalinski L
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2014
- Field of study
The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV
Evolutionary Dynamics Analysis of Human Metapneumovirus Subtype A2: Genetic Evidence for Its Dominant Epidemic
- Author
- A Padhi
- A Sarasini
- AJ Drummond
- B Huck
- BG van den Hoogen
- D Posada
- DB Oliveira
- DE Noyola
- E Agapov
- E Agapov
- EC Holmes
- G Gerna
- G Zehender
- Gláucia Paranhos-Baccalà
- Guy Vernet
- HP Ludewick
- IM Mackay
- JC Wilgenbusch
- Jianguo Li
- Jianwei Wang
- JS Kahn
- JY Chung
- K Pan
- K Tamura
- KK Tee
- L Ren
- L Ren
- Li Guo
- Lijun Rong
- Lili Ren
- M de Graaf
- M El Sayed Zaki
- N Bastien
- N Ishiguro
- OG Pybus
- P Lemey
- R Dolz
- S Ahumada-Ruiz
- S Biacchesi
- S Biacchesi
- S Caracciolo
- SL Pond
- TC Peret
- TC Peret
- TC Peret
- TP Sloots
- YC Liao
- YI Wolf
- Z Yang
- Zichun Xiang
- Publication venue
- Public Library of Science
- Publication date
- 30/03/2012
- Field of study
Human metapneumovirus (hMPV) is a respiratory viral pathogen in children worldwide. hMPV is divided into four subtypes: hMPV_A1, hMPV_A2, hMPV_B1, and hMPV_B2. hMPV_A2 can be further divided into hMPV_A2a and A2b based on phylogenetic analysis. The typical prevalence pattern of hMPV involves a shift of the predominant subtype within one or two years. However, hMPV_A2, in particular hMPV_A2b, has circulated worldwide with a several years long term high epidemic. To study this distinct epidemic behavior of hMPV_A2, we analyzed 294 sequences of partial G genes of the virus from different countries. Molecular evolutionary data indicates that hMPV_A2 evolved toward heterogeneity faster than the other subtypes. Specifically, a Bayesian skyline plot analysis revealed that hMPV_A2 has undergone a generally upward fluctuation since 1997, whereas the other subtypes experienced only one upward fluctuation. Although hMPV_A2 showed a lower value of mean dN/dS than the other subtypes, it had the largest number of positive selection sites. Meanwhile, various styles of mutation were observed in the mutation hotspots of hMPV_A2b. Bayesian phylogeography analysis also revealed two fusions of diffusion routes of hMPV_A2b in India (June 2006) and Beijing, China (June 2008). Sequences of hMPV_A2b retrieved from GenBank boosted simultaneously with the two fusions respectively, indicating that fusion of genetic transmission routes from different regions improved survival of hMPV_A2. Epidemic and evolutionary dynamics of hMPV_A2b were similar to those of hMPV_A2. Overall, our findings provide important molecular insights into hMPV epidemics and viral variation, and explain the occurrence of an atypical epidemic of hMPV_A2, particularly hMPV_A2b
The Evolution of the Major Hepatitis C Genotypes Correlates with Clinical Response to Interferon Therapy
- Author
- A Mangia
- A Stamatakis
- A Zekry
- AB Hill
- AL Cox
- AR El-Zayadi
- AR Lloyd
- AS Muerhoff
- B Gao
- B Kolaczkowski
- BT Grenfell
- C Combet
- C Gaudy
- C Kuiken
- D Agosti
- DB Smith
- DB Smith
- DJ Zwickl
- DJ Zwickl
- DL Swofford
- DM Hillis
- DR Taylor
- DS Sikes
- E Jaeckel
- EC Holmes
- EC Verna
- EH Sklan
- F Dal Pero
- F Hasan
- F McOmish
- FV Chisari
- FZ Alfaleh
- G Magiorkinis
- G Szabo
- H Shimodaira
- H Shimodaira
- J Felsenstein
- J Felsenstein
- J Timm
- JD Thompson
- Jeffrey S. Glenn
- JJ Feld
- JJ Feld
- JQ Han
- JQ Han
- K Katoh
- KC Nixon
- L Rubbia-Brandt
- M Derbala
- M Dimitrova
- M Miyamoto
- M Salemi
- M Sarasin-Filipowicz
- M von Wagner
- M von Wagner
- M Gale Jr.
- MG Katze
- MG Rumi
- MJ Gale Jr
- ML Shiffman
- ML Shiffman
- ML Shiffman
- ML Yu
- MP Manns
- MW Fried
- N Antaki
- N Coppola
- N Enomoto
- N Kato
- N Ogata
- NA Cannon
- O Dalgard
- OG Pybus
- OG Pybus
- OG Pybus
- P Farci
- P Farci
- P Munoz de Rueda
- P Simmonds
- P Simmonds
- P Simmonds
- P Simmonds
- Paul J. Planet
- PH Harvey
- Phillip S. Pang
- PJ Planet
- PJ Planet
- R Aurora
- R Bartenschlager
- R DeSalle
- S Chevaliez
- S Zeuzem
- SC Ray
- Sheila Mary Bowyer
- SI Khakoo
- SJ Hadziyannis
- SL Fishman
- SL Pond
- SM Kamal
- SM Kamal
- SM Kamal
- SM Kamal
- T Berg
- T Eriksson
- T Kuntzen
- T Noguchi
- WM Fitch
- WP Hofmann
- WP Maddison
- XS He
- Z Chen
- Publication venue
- Public Library of Science
- Publication date
- 01/08/2009
- Field of study
Patients chronically infected with hepatitis C virus (HCV) require significantly different durations of therapy and achieve substantially different sustained virologic response rates to interferon-based therapies, depending on the HCV genotype with which they are infected. There currently exists no systematic framework that explains these genotype-specific response rates. Since humans are the only known natural hosts for HCV-a virus that is at least hundreds of years old-one possibility is that over the time frame of this relationship, HCV accumulated adaptive mutations that confer increasing resistance to the human immune system. Given that interferon therapy functions by triggering an immune response, we hypothesized that clinical response rates are a reflection of viral evolutionary adaptations to the immune system.We have performed the first phylogenetic analysis to include all available full-length HCV genomic sequences (n = 345). This resulted in a new cladogram of HCV. This tree establishes for the first time the relative evolutionary ages of the major HCV genotypes. The outcome data from prospective clinical trials that studied interferon and ribavirin therapy was then mapped onto this new tree. This mapping revealed a correlation between genotype-specific responses to therapy and respective genotype age. This correlation allows us to predict that genotypes 5 and 6, for which there currently are no published prospective trials, will likely have intermediate response rates, similar to genotype 3. Ancestral protein sequence reconstruction was also performed, which identified the HCV proteins E2 and NS5A as potential determinants of genotype-specific clinical outcome. Biochemical studies have independently identified these same two proteins as having genotype-specific abilities to inhibit the innate immune factor double-stranded RNA-dependent protein kinase (PKR).An evolutionary analysis of all available HCV genomes supports the hypothesis that immune selection was a significant driving force in the divergence of the major HCV genotypes and that viral factors that acquired the ability to inhibit the immune response may play a role in determining genotype-specific response rates to interferon therapy
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