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Weiler, A.

Publications and source records attributed to Weiler, A..

2 recordsLinked to original sources

Zika viruses of both African and Asian lineages cause fetal harm in a vertical transmission model

Congenital Zika virus (ZIKV) infection was first linked to birth defects during the American outbreak 1-3. It has been proposed that mutations unique to the Asian/American-genotype explain, at least in part, the ability of Asian/American ZIKV to cause congenital Zika syndrome (CZS) 4,5. Recent studies identified mutations in ZIKV infecting humans that arose coincident with the outbreak in French Polynesia and were stably maintained during subsequent spread to the Americas 5. Here we show that African ZIKV can infect and harm fetuses and that the S139N mutation that has been associated with the American outbreak is not essential for fetal harm. Our findings, in a vertical transmission mouse model, suggest that ZIKV will remain a threat to pregnant women for the foreseeable future, including in Africa, southeast Asia, and the Americas. Additional research is needed to better understand the risks associated with ZIKV infection during pregnancy, both in areas where the virus is newly endemic and where it has been circulating for decades.

microbiology

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

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.

microbiology