Molecularly barcoded Zika virus libraries to probe in vivo evolutionary dynamics

被引:28
作者
Aliota, Matthew T. [1 ]
Dudley, Dawn M. [2 ]
Newman, Christina M. [2 ]
Weger-Lucarelli, James [3 ,7 ]
Stewart, Laurel M. [2 ]
Koenig, Michelle R. [2 ]
Breitbach, Meghan E. [2 ]
Weiler, Andrea M. [4 ]
Semler, Matthew R. [2 ]
Barry, Gabrielle L. [4 ]
Zarbock, Katie R. [4 ]
Haj, Amelia K. [2 ]
Moriarty, Ryan V. [4 ]
Mohns, Martel S. [2 ]
Mohr, Emma L. [5 ]
Venturi, Vanessa [6 ]
Schultz-Darken, Nancy [4 ]
Peterson, Eric [4 ]
Newton, Wendy [4 ]
Schotzko, Michele L. [4 ]
Simmons, Heather A. [4 ]
Mejia, Andres [4 ]
Hayes, Jennifer M. [4 ]
Capuano, Saverio, III [4 ]
Davenport, Miles P. [6 ]
Friedrich, Thomas C. [1 ,4 ]
Ebel, Gregory D. [3 ]
O'Connor, Shelby L. [2 ,4 ]
O'Connor, David H. [2 ,4 ]
机构
[1] Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53706 USA
[2] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA
[3] Colorado State Univ, Arthropod Borne & Infect Dis Lab, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA
[4] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53706 USA
[5] Univ Wisconsin, Dept Pediat, Madison, WI USA
[6] Univ New South Wales, Kirby Inst Infect & Immun, Infect Analyt Program, Sydney, NSW, Australia
[7] Inst Pasteur, Viral Populat & Pathogenesis Unit, Paris, France
基金
美国国家卫生研究院;
关键词
VERTICAL TRANSMISSION; CULEX-PIPIENS; INFECTION; STRAIN; RNA; BOTTLENECKS; GENOME;
D O I
10.1371/journal.ppat.1006964
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Defining the complex dynamics of Zika virus (ZIKV) infection in pregnancy and during transmission between vertebrate hosts and mosquito vectors is critical for a thorough understanding of viral transmission, pathogenesis, immune evasion, and potential reservoir establishment. Within-host viral diversity in ZIKV infection is low, which makes it difficult to evaluate infection dynamics. To overcome this biological hurdle, we constructed a molecularly barcoded ZIKV. This virus stock consists of a "synthetic swarm" whose members are genetically identical except for a run of eight consecutive degenerate codons, which creates approximately 64,000 theoretical nucleotide combinations that all encode the same amino acids. Deep sequencing this region of the ZIKV genome enables counting of individual barcodes to quantify the number and relative proportions of viral lineages present within a host. Here we used these molecularly barcoded ZIKV variants to study the dynamics of ZIKV infection in pregnant and non-pregnant macaques as well as during mosquito infection/transmission. The barcoded virus had no discernible fitness defects in vivo, and the proportions of individual barcoded virus templates remained stable throughout the duration of acute plasma viremia. ZIKV RNA also was detected in maternal plasma from a pregnant animal infected with barcoded virus for 67 days. The complexity of the virus population declined precipitously 8 days following infection of the dam, consistent with the timing of typical resolution of ZIKV in non-pregnant macaques and remained low for the subsequent duration of viremia. Our approach showed that synthetic swarm viruses can be used to probe the composition of ZIKV populations over time in vivo to understand vertical transmission, persistent reservoirs, bottlenecks, and evolutionary dynamics.
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页数:25
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