Genetic Drift during Systemic Arbovirus Infection of Mosquito Vectors Leads to Decreased Relative Fitness during Host Switching

Grubaugh, Nathan D.; Weger-Lucarelli, James; Murrieta, Reyes A.; Fauver, Joseph R.; Garcia-Luna, Selene; Prasad, Abhishek N.; Black, William C.; Ebel, Gregory D.

doi:10.1016/j.chom.2016.03.002

Cited by 128 publications

(171 citation statements)

References 50 publications

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“…We found no 216 evidence that selection favored specific variants in mosquito transmission; instead, we observed 217 a more heterogeneous distribution of viral SNPs in mosquito-infected monkeys than in sc-218 inoculated animals. These findings are consistent with the observation that arboviruses undergo 219 multiple population bottlenecks in infected mosquitoes 30,31 ; as a result, different mosquitoes 220 could transmit different founder populations to different macaques. The low number of viral 221 genome copies isolated from mosquito saliva, together with the differing patterns of SNPs 222 observed among mosquito-bitten macaques, are also consistent with the interpretation that 223 mosquito transmission involves a random viral population bottleneck.…”

Section: Cc-by-nc-nd 40 International License Peer-reviewed) Is Thesupporting

confidence: 84%

“…Also, during replication in mosquitoes, flaviviruses 160 undergo population bottlenecks as they traverse physical barriers like the midgut 30,31 . We 161 therefore reasoned that viral genetic diversity in mosquitoes and monkeys infected by mosquito 162 bite would be low as compared with the virus stock and populations in sc-inoculated monkeys.…”

Section: Results 79mentioning

confidence: 99%

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Infection via mosquito bite alters Zika virus replication kinetics in rhesus macaques

Lalli

et al. 2017

Preprint

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For more than three decades it has been recognized that small amounts of vector saliva can significantly alter the infectivity of vector-borne pathogens and subsequent in vivo dynamics. Mouse and nonhuman primate models now serve as useful platforms to study Zika virus (ZIKV) pathogenesis, candidate therapies, and vaccines, but they rely on needle inoculation of virus: the effects of mosquito-borne infection on disease outcome have not been explored in these models. To model vector-borne transmission of ZIKV in nonhuman primates, we infected Aedes aegypti mosquitoes with ZIKV and allowed them to feed on four ZIKV-naive rhesus macaques. We compared ZIKV replication kinetics and tissue distribution between animals that were subcutaneously inoculated with 104 plaque-forming units of ZIKV and those that were exposed via mosquito bite. Here, we show that infection via mosquito bite delays ZIKV replication to peak viral loads in rhesus macaques. Importantly, in mosquito-infected animals ZIKV tissue distribution was limited to hemolymphatic tissues, female reproductive tract tissues, kidney, and liver, potentially emulating key features of human ZIKV infections, most of which are characterized by mild or asymptomatic disease. This newly developed system will be valuable for studying ZIKV disease because it more closely mimics human infection by mosquito bite than needle-based inoculations.

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Section: Cc-by-nc-nd 40 International License Peer-reviewed) Is Thesupporting

confidence: 84%

Section: Results 79mentioning

confidence: 99%

Infection via mosquito bite alters Zika virus replication kinetics in rhesus macaques

Lalli

et al. 2017

Preprint

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show abstract

“…An overlapping region of the genome is found in both plasmids, allowing the 5= and 3= portions of the viral genome to be conjoined following digestion with ApaLI and SapI. The sequence for the T7 promoter and hepatitis D virus ribozyme were previously cloned into a West Nile virus infectious clone (19). Clones with the correct restriction pattern were verified by sequencing, and correct clones were selected for virus rescue.…”

Section: Methodsmentioning

confidence: 99%

Development and Characterization of Recombinant Virus Generated from a New World Zika Virus Infectious Clone

Weger-Lucarelli

Duggal

Bullard-Feibelman

et al. 2017

J Virol

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112

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Zika virus (ZIKV; family Flaviviridae, genus Flavivirus) is a rapidly expanding global pathogen that has been associated with severe clinical manifestations, including devastating neurological disease in infants. There are currently no molecular clones of a New World ZIKV available that lack significant attenuation, hindering progress toward understanding determinants of transmission and pathogenesis. Here we report the development and characterization of a novel ZIKV reverse genetics system based on a 2015 isolate from Puerto Rico (PRVABC59). We generated a two-plasmid infectious clone system from which infectious virus was rescued that replicates in human and mosquito cells with growth kinetics representative of wildtype ZIKV. Infectious clone-derived virus initiated infection and transmission rates in Aedes aegypti mosquitoes comparable to those of the primary isolate and displayed similar pathogenesis in AG129 mice. This infectious clone system provides a valuable resource to the research community to explore ZIKV molecular biology, vaccine development, antiviral development, diagnostics, vector competence, and disease pathogenesis.IMPORTANCE ZIKV is a rapidly spreading mosquito-borne pathogen that has been linked to Guillain-Barré syndrome in adults and congenital microcephaly in developing fetuses and infants. ZIKV can also be sexually transmitted. The viral molecular determinants of any of these phenotypes are not well understood. There is no reverse genetics system available for the current epidemic virus that will allow researchers to study ZIKV immunity, develop novel vaccines, or develop antiviral drugs. Here we provide a novel infectious clone system generated from a recent ZIKV isolated from a patient infected in Puerto Rico. This infectious clone produces virus with in vitro and in vivo characteristics similar to those of the primary isolate, providing a critical tool to study ZIKV infection and disease.

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“…tarsalis mosquitoes with ZIKV. The laboratory colonies used here; despite extensive time in colony, have been used at length for WNV experimentation with high infection, dissemination and transmission rates, providing evidence that they are not generally refractory to flavivirus infection [48]. Further, field populations of Cx .…”

Section: Discussionmentioning

confidence: 99%

Vector Competence of American Mosquitoes for Three Strains of Zika Virus

et al. 2016

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In 2015, Zika virus (ZIKV; Flaviviridae; Flavivirus) emerged in the Americas, causing millions of infections in dozens of countries. The rapid spread of the virus and the association with disease outcomes such as Guillain-Barré syndrome and microcephaly make understanding transmission dynamics essential. Currently, there are no reports of vector competence (VC) of American mosquitoes for ZIKV isolates from the Americas. Further, it is not clear whether ZIKV strains from other genetic lineages can be transmitted by American Aedes aegypti populations, and whether the scope of the current epidemic is in part facilitated by viral factors such as enhanced replicative fitness or increased vector competence. Therefore, we characterized replication of three ZIKV strains, one from each of the three phylogenetic clades in several cell lines and assessed their abilities to be transmitted by Ae. aegypti mosquitoes. Additionally, laboratory colonies of different Culex spp. were infected with an American outbreak strain of ZIKV to assess VC. Replication rates were variable and depended on virus strain, cell line and MOI. African strains used in this study outcompeted the American strain in vitro in both mammalian and mosquito cell culture. West and East African strains of ZIKV tested here were more efficiently transmitted by Ae. aegypti from Mexico than was the currently circulating American strain of the Asian lineage. Long-established laboratory colonies of Culex mosquitoes were not efficient ZIKV vectors. These data demonstrate the capacity for additional ZIKV strains to infect and replicate in American Aedes mosquitoes and suggest that neither enhanced virus replicative fitness nor virus adaptation to local vector mosquitoes seems likely to explain the extent and intensity of ZIKV transmission in the Americas.

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Genetic Drift during Systemic Arbovirus Infection of Mosquito Vectors Leads to Decreased Relative Fitness during Host Switching

Cited by 128 publications

References 50 publications

Infection via mosquito bite alters Zika virus replication kinetics in rhesus macaques

Infection via mosquito bite alters Zika virus replication kinetics in rhesus macaques

Development and Characterization of Recombinant Virus Generated from a New World Zika Virus Infectious Clone

Vector Competence of American Mosquitoes for Three Strains of Zika Virus

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