Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence

被引:91
作者
Brook, Cara E. [1 ,2 ]
Boots, Mike [1 ]
Chandran, Kartik [3 ]
Dobson, Andrew P. [2 ]
Drosten, Christian [4 ,5 ,6 ,7 ]
Graham, Andrea L. [2 ]
Grenfell, Bryan T. [2 ,8 ]
Mueller, Marcel A. [4 ,5 ,6 ,7 ,9 ]
Ng, Melinda [3 ]
Wang, Lin-Fa [10 ]
van Leeuwen, Anieke [2 ,11 ]
机构
[1] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA
[2] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA
[3] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA
[4] Charite Univ Med Berlin, Inst Virol, Berlin, Germany
[5] Free Univ Berlin, Berlin, Germany
[6] Humboldt Univ, Berlin, Germany
[7] Berlin Inst Hlth, Berlin, Germany
[8] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA
[9] Sechenov Univ, Martsinovsky Inst Med Parasitol Trop & Vector Bor, Moscow, Russia
[10] Duke Natl Univ Singapore, Emerging Infect Dis Program, Med Sch, Singapore, Singapore
[11] Univ Utrecht, Royal Netherlands Inst Sea Res, Dept Coastal Syst, Den Burg, Netherlands
来源
ELIFE | 2020年 / 9卷
基金
美国国家卫生研究院; 新加坡国家研究基金会; 欧盟地平线“2020”; 美国国家科学基金会;
关键词
IN-VIVO; ANTIVIRAL STATE; VIRUS-INFECTION; INTERFERON; ESTABLISHMENT; PATHOGENESIS; REPLICATION; EXPRESSION; RESERVOIRS; PATHOLOGY;
D O I
10.7554/eLife.48401
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Bats host virulent zoonotic viruses without experiencing disease. A mechanistic understanding of the impact of bats' virus hosting capacities, including uniquely constitutive immune pathways, on cellular-scale viral dynamics is needed to elucidate zoonotic emergence. We carried out virus infectivity assays on bat cell lines expressing induced and constitutive immune phenotypes, then developed a theoretical model of our in vitro system, which we fit to empirical data. Best fit models recapitulated expected immune phenotypes for representative cell lines, supporting robust antiviral defenses in bat cells that correlated with higher estimates for within-host viral propagation rates. In general, heightened immune responses limit pathogen-induced cellular morbidity, which can facilitate the establishment of rapidly-propagating persistent infections within-host. Rapidly-transmitting viruses that have evolved with bat immune systems will likely cause enhanced virulence following emergence into secondary hosts with immune systems that diverge from those unique to bats.
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页数:24
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