Host genetic barriers to virus spillover

病毒溢出的宿主遗传屏障

• 批准号: 10310462
• 负责人: Sara Sawyer
• 金额: $ 41.35万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-10 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10310462
• 关键词: African; Alleles; Animals; Arenavirus; Avian Influenza A Virus; Biocompatible Materials; Biological Assay; CCR5 gene; CD4 Antigens; Canine Parvovirus; Canis familiaris; Cell Surface Receptors; Cells; Data; Dengue Virus; Disease; Ebola virus; Epidemic; Event; Evolution; Genetic; Genetic Polymorphism; Genetic Variation; Genotype; Goals; HIV; HIV Receptors; Housing; Human; Individual; Infection; Lentivirus; Middle East Respiratory Syndrome Coronavirus; Modeling; Mutation; Nature; Orthologous Gene; Play; Population; Predisposition; Primate Lentiviruses; Primates; Process; Property; Research; Rodent; Role; SARS coronavirus; SIV; Surveys; Testing; Variant; Viral; Viral Genome; Viral reservoir; Virus; Work; Zika Virus; base; cross-species transmission; experimental study; fitness; innovation; novel; pet animal; prevent; receptor; simian human immunodeficiency virus; spillover event; transmission process

Project Summary     Viruses  exploit  cell  surface  receptors  to  gain  access  to  the  interior  of  host  cells.  These  receptors  are  now  appreciated as major obstacles to virus spillover, a process by which animal viruses move from one host species  into another. In the many documented examples of spillover, viruses typically use the same entry receptor in the  old  and  new  host,  but  need  to  acquire  mutations  to  make  them  compatible  with  the  specific  ortholog  of  that  receptor  found  in  the  new  host.  Diverse  viruses  such  as  avian  influenza  viruses,  rodent  arenaviruses,  MERS  coronavirus, and possibly SARS and Ebola viruses all overcame receptor barriers in humans as they transmitted  from  their  animal  hosts.  Here,  we  explore  the  following  hypothesis  of  disease  emergence:  viruses  can  more  easily  overcome  receptor  barriers  when  host  individuals  of  specific  receptor  genotypes  come  into  contact. We use the simian immunodeficiency virus (SIV) reservoir in African primates as a model for this, and  investigate the role that the SIV/HIV receptors, CD4 and CCR5, play in limiting spillover of these viruses. Primate  lentiviruses (SIV/HIV) are an excellent model because the HIV/SIV receptors CD4 and CCR5 serve as significant  host barriers to the spillover of these viruses between primate species. We and others have shown that (1) CD4  and CCR5 vary from one species to the next in their ability to serve as receptors for HIV/SIV, and (2) different  individuals  within  primate  populations  have  different  virus  susceptibilities  because  of  receptor  polymorphisms.  We leverage genetic data and biomaterials from approximately 1,300 primates representing 15 different species,  and  a  broad  array  of  different  HIV  and  SIV  variants,  to  test  the  idea  that  certain  individuals  within  populations  are better poised to transmit or receive infection during spillover scenarios. The main innovation of the proposal  is  to  define  the  role  of  host  genetic  variation  in  disease  emergence,  beyond  a  strict  focus  on  the  evolutionary  properties  of  viruses.  The  project  will  aid  in  our  understanding  of  the  evolutionary  processes  leading  to  the  emergence of new diseases. It is significant because the work here will be widely applicable to diverse viruses  beyond lentiviruses, and to host barriers beyond receptor blocks.

项目总结

项目成果

Positive natural selection in primate genes of the type I interferon response.

• DOI: 10.1186/s12862-021-01783-z
• 发表时间: 2021-04-26
• 期刊: BMC ecology and evolution
• 影响因子: 2.2
• 作者: Judd EN;Gilchrist AR;Meyerson NR;Sawyer SL
• 通讯作者: Sawyer SL

Monkeypox emergency: Urgent questions and perspectives.

• DOI: 10.1016/j.cell.2022.08.002
• 发表时间: 2022-09-01
• 期刊: CELL
• 影响因子: 64.5
• 作者: Rothenburg, Stefan;Yang, Zhilong;Beard, Pip;Sawyer, Sara L.;Titanji, Boghuma;Gonsalves, Gregg;Kindrachuk, Jason
• 通讯作者: Kindrachuk, Jason

RNase L limits host and viral protein synthesis via inhibition of mRNA export.

• DOI: 10.1126/sciadv.abh2479
• 发表时间: 2021-06
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Burke JM;Gilchrist AR;Sawyer SL;Parker R
• 通讯作者: Parker R

TRIM5α Restricts Flavivirus Replication by Targeting the Viral Protease for Proteasomal Degradation.

• DOI: 10.1016/j.celrep.2019.05.040
• 发表时间: 2019-06-11
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Chiramel AI;Meyerson NR;McNally KL;Broeckel RM;Montoya VR;Méndez-Solís O;Robertson SJ;Sturdevant GL;Lubick KJ;Nair V;Youseff BH;Ireland RM;Bosio CM;Kim K;Luban J;Hirsch VM;Taylor RT;Bouamr F;Sawyer SL;Best SM
• 通讯作者: Best SM

Saliva TwoStep for rapid detection of asymptomatic SARS-CoV-2 carriers.

• DOI: 10.7554/elife.65113
• 发表时间: 2021-03-29
• 期刊: eLife
• 影响因子: 7.7
• 作者: Yang Q;Meyerson NR;Clark SK;Paige CL;Fattor WT;Gilchrist AR;Barbachano-Guerrero A;Healy BG;Worden-Sapper ER;Wu SS;Muhlrad D;Decker CJ;Saldi TK;Lasda E;Gonzales P;Fink MR;Tat KL;Hager CR;Davis JC;Ozeroff CD;Brisson GR;McQueen MB;Leinwand LA;Parker R;Sawyer SL
• 通讯作者: Sawyer SL