Abstract
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. 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. Furthermore, deep sequencing analysis reveals that ZIKV populations in mosquito-infected monkeys show greater sequence heterogeneity and lower overall diversity than in needle-inoculated animals. 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.
Highlights
Mouse and nonhuman primate models 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
Viral passage from mice through mosquitoes to macaques appeared to alter the frequencies of single-nucleotide polymorphisms (SNPs) in the ZIKV population as compared with the stock virus
The low number of viral genome copies isolated from mosquito saliva, together with the differing patterns of SNPs observed among mosquito-bitten macaques, are consistent with the interpretation that transmission between mammalian hosts via mosquitoes involves one or more random viral population bottlenecks
Summary
Mouse and nonhuman primate models 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 assess differences in ZIKV replication between virus delivery by needle vs mosquito vector, we infected rhesus macaques with the Puerto Rican ZIKV isolate PRVABC59 by either sc inoculation (n = 3) or by exposure to infected mosquitoes (n = 4).
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