Molecular and Fitness Barriers to Bunyavirus Reassortment

布尼亚病毒重组的分子和适应性障碍

基本信息

  • 批准号:
    10719791
  • 负责人:
  • 金额:
    $ 41.9万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-08-10 至 2028-07-31
  • 项目状态:
    未结题

项目摘要

Project Summary / Abstract The bunyavirus order (Bunyavirales) includes significant human, animal, and plant pathogens. As with all segmented viruses, reassortment is a major driver of bunyavirus evolution. Reassortment can produce viruses with undesirable phenotypes, including the ability to infect new hosts. As the world becomes increasingly interconnected and disrupted by climate change, the opportunity for previously isolated bunyaviruses to meet and reassort is increasing. Compatibility between the proteins and RNAs of two viruses is a key determinant of whether they can produce viable reassortant progeny. And, because reassortment joins proteins and RNAs that have not adapted to work together, new reassortants face an uphill evolutionary battle when competing with their parents and other viruses in the population. This proposal will generate an improved mechanistic understanding of molecular barriers to reassortment and investigate evolutionary pathways that permit reassortants to emerge despite initial fitness disadvantages. We have devised a new system that uses libraries of competing minigenomes to quantify reassortment potential between large numbers of viruses simultaneously, and to define the molecular breakdown in cases when they can’t. Using these “minigenome melees” in concert with traditional techniques, we propose to answer targeted questions about the molecular compatibility between bunyaviruses. Our team combines expertise in viral genomics, molecular virology, mosquito infection, and virus evolution. In aim 1, we identify steps in the viral lifecycle that break down when bunyavirus replication proteins are mismatched and perform directed evolution experiments that force mismatched proteins to adapt to work together. This will explain a key constraint on bunyavirus reassortment and detail molecular interactions at the heart of the bunyavirus life cycle. In aim 2, we use our minigenome melee system to test the hypothesis that orthobunyavirus reassortment is relatively unconstrained by packaging. In aim 3, we test the hypothesis that bottlenecks associated with replication in mosquitoes enable less fit reassortant genotypes to gain a foothold in populations via the stochastic effect of genetic drift. At the conclusion of this project, we expect to have a substantially improved understanding of the molecular rules that determine whether two bunyaviruses can reassort, the fitness consequences of reassortment, and the evolutionary pathways by which reassortant viruses emerge. Our results could be used to parameterize models that predict bunyavirus emergence risk and will shed light on conserved interactions that could be targeted by antiviral drugs. Minigenome melees could in principle be used to study the biology and evolution of all kinds of RNA viruses, and we expect this work to establish this as a broadly useful platform.
项目摘要/摘要

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Mark D. Stenglein其他文献

Taxonomy of the order Bunyavirales: second update 2018
  • DOI:
    10.1007/s00705-018-04127-3
  • 发表时间:
    2019-01-20
  • 期刊:
  • 影响因子:
    2.500
  • 作者:
    Piet Maes;Scott Adkins;Sergey V. Alkhovsky;Tatjana Avšič-Županc;Matthew J. Ballinger;Dennis A. Bente;Martin Beer;Éric Bergeron;Carol D. Blair;Thomas Briese;Michael J. Buchmeier;Felicity J. Burt;Charles H. Calisher;Rémi N. Charrel;Il Ryong Choi;J. Christopher S. Clegg;Juan Carlos de la Torre;Xavier de Lamballerie;Joseph L. DeRisi;Michele Digiaro;Mike Drebot;Hideki Ebihara;Toufic Elbeaino;Koray Ergünay;Charles F. Fulhorst;Aura R. Garrison;George Fú Gāo;Jean-Paul J. Gonzalez;Martin H. Groschup;Stephan Günther;Anne-Lise Haenni;Roy A. Hall;Roger Hewson;Holly R. Hughes;Rakesh K. Jain;Miranda Gilda Jonson;Sandra Junglen;Boris Klempa;Jonas Klingström;Richard Kormelink;Amy J. Lambert;Stanley A. Langevin;Igor S. Lukashevich;Marco Marklewitz;Giovanni P. Martelli;Nicole Mielke-Ehret;Ali Mirazimi;Hans-Peter Mühlbach;Rayapati Naidu;Márcio Roberto Teixeira Nunes;Gustavo Palacios;Anna Papa;Janusz T. Pawęska;Clarence J. Peters;Alexander Plyusnin;Sheli R. Radoshitzky;Renato O. Resende;Víctor Romanowski;Amadou Alpha Sall;Maria S. Salvato;Takahide Sasaya;Connie Schmaljohn;Xiǎohóng Shí;Yukio Shirako;Peter Simmonds;Manuela Sironi;Jin-Won Song;Jessica R. Spengler;Mark D. Stenglein;Robert B. Tesh;Massimo Turina;Tàiyún Wèi;Anna E. Whitfield;Shyi-Dong Yeh;F. Murilo Zerbini;Yong-Zhen Zhang;Xueping Zhou;Jens H. Kuhn
  • 通讯作者:
    Jens H. Kuhn
2020 taxonomic update for phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales
  • DOI:
    10.1007/s00705-020-04731-2
  • 发表时间:
    2020-09-04
  • 期刊:
  • 影响因子:
    2.500
  • 作者:
    Jens H. Kuhn;Scott Adkins;Daniela Alioto;Sergey V. Alkhovsky;Gaya K. Amarasinghe;Simon J. Anthony;Tatjana Avšič-Županc;María A. Ayllón;Justin Bahl;Anne Balkema-Buschmann;Matthew J. Ballinger;Tomáš Bartonička;Christopher Basler;Sina Bavari;Martin Beer;Dennis A. Bente;Éric Bergeron;Brian H. Bird;Carol Blair;Kim R. Blasdell;Steven B. Bradfute;Rachel Breyta;Thomas Briese;Paul A. Brown;Ursula J. Buchholz;Michael J. Buchmeier;Alexander Bukreyev;Felicity Burt;Nihal Buzkan;Charles H. Calisher;Mengji Cao;Inmaculada Casas;John Chamberlain;Kartik Chandran;Rémi N. Charrel;Biao Chen;Michela Chiumenti;Il-Ryong Choi;J. Christopher S. Clegg;Ian Crozier;John V. da Graça;Elena Dal Bó;Alberto M. R. Dávila;Juan Carlos de la Torre;Xavier de Lamballerie;Rik L. de Swart;Patrick L. Di Bello;Nicholas Di Paola;Francesco Di Serio;Ralf G. Dietzgen;Michele Digiaro;Valerian V. Dolja;Olga Dolnik;Michael A. Drebot;Jan Felix Drexler;Ralf Dürrwald;Lucie Dufkova;William G. Dundon;W. Paul Duprex;John M. Dye;Andrew J. Easton;Hideki Ebihara;Toufic Elbeaino;Koray Ergünay;Jorlan Fernandes;Anthony R. Fooks;Pierre B. H. Formenty;Leonie F. Forth;Ron A. M. Fouchier;Juliana Freitas-Astúa;Selma Gago-Zachert;George Fú Gāo;María Laura García;Adolfo García-Sastre;Aura R. Garrison;Aiah Gbakima;Tracey Goldstein;Jean-Paul J. Gonzalez;Anthony Griffiths;Martin H. Groschup;Stephan Günther;Alexandro Guterres;Roy A. Hall;John Hammond;Mohamed Hassan;Jussi Hepojoki;Satu Hepojoki;Udo Hetzel;Roger Hewson;Bernd Hoffmann;Seiji Hongo;Dirk Höper;Masayuki Horie;Holly R. Hughes;Timothy H. Hyndman;Amara Jambai;Rodrigo Jardim;Dàohóng Jiāng;Qi Jin;Gilda B. Jonson;Sandra Junglen;Serpil Karadağ;Karen E. Keller;Boris Klempa;Jonas Klingström;Gary Kobinger;Hideki Kondō;Eugene V. Koonin;Mart Krupovic;Gael Kurath;Ivan V. Kuzmin;Lies Laenen;Robert A. Lamb;Amy J. Lambert;Stanley L. Langevin;Benhur Lee;Elba R. S. Lemos;Eric M. Leroy;Dexin Li;Jiànróng Lǐ;Mifang Liang;Wénwén Liú;Yàn Liú;Igor S. Lukashevich;Piet Maes;William Marciel de Souza;Marco Marklewitz;Sergio H. Marshall;Giovanni P. Martelli;Robert R. Martin;Shin-Yi L. Marzano;Sébastien Massart;John W. McCauley;Nicole Mielke-Ehret;Angelantonio Minafra;Maria Minutolo;Ali Mirazimi;Hans-Peter Mühlbach;Elke Mühlberger;Rayapati Naidu;Tomohide Natsuaki;Beatriz Navarro;José A. Navarro;Sergey V. Netesov;Gabriele Neumann;Norbert Nowotny;Márcio R. T. Nunes;Are Nylund;Arnfinn L. Økland;Renata C. Oliveira;Gustavo Palacios;Vicente Pallas;Bernadett Pályi;Anna Papa;Colin R. Parrish;Alex Pauvolid-Corrêa;Janusz T. Pawęska;Susan Payne;Daniel R. Pérez;Florian Pfaff;Sheli R. Radoshitzky;Aziz-ul Rahman;Pedro L. Ramos-González;Renato O. Resende;Carina A. Reyes;Bertus K. Rima;Víctor Romanowski;Gabriel Robles Luna;Paul Rota;Dennis Rubbenstroth;Jonathan A. Runstadler;Daniel Ruzek;Sead Sabanadzovic;Jiří Salát;Amadou Alpha Sall;Maria S. Salvato;Kamil Sarpkaya;Takahide Sasaya;Martin Schwemmle;Muhammad Z. Shabbir;Xiǎohóng Shí;Zhènglì Shí;Yukio Shirako;Peter Simmonds;Jana Širmarová;Manuela Sironi;Sophie Smither;Teemu Smura;Jin-Won Song;Kirsten M. Spann;Jessica R. Spengler;Mark D. Stenglein;David M. Stone;Petra Straková;Ayato Takada;Robert B. Tesh;Natalie J. Thornburg;Keizō Tomonaga;Noël Tordo;Jonathan S. Towner;Massimo Turina;Ioannis Tzanetakis;Rainer G. Ulrich;Anna Maria Vaira;Bernadette van den Hoogen;Arvind Varsani;Nikos Vasilakis;Martin Verbeek;Victoria Wahl;Peter J. Walker;Hui Wang;Jianwei Wang;Xifeng Wang;Lin-Fa Wang;Tàiyún Wèi;Heather Wells;Anna E. Whitfield;John V. Williams;Yuri I. Wolf;Zhìqiáng Wú;Xin Yang;Xīnglóu Yáng;Xuejie Yu;Natalya Yutin;F. Murilo Zerbini;Tong Zhang;Yong-Zhen Zhang;Guohui Zhou;Xueping Zhou
  • 通讯作者:
    Xueping Zhou

Mark D. Stenglein的其他文献

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