التفاصيل البيبلوغرافية
| العنوان: |
Two Sides of a Coin: a Zika Virus Mutation Selected in Pregnant Rhesus Macaques Promotes Fetal Infection in Mice but at a Cost of Reduced Fitness in Nonpregnant Macaques and Diminished Transmissibility by Vectors. |
| المؤلفون: |
Lemos, Danilo1, Stuart, Jackson B.1, Louie, William1, Singapuri, Anil1, Ramírez, Ana L.1, Watanabe, Jennifer2, Usachenko, Jodie2, Keesler, Rebekah I.2, Martin, Claudia Sanchez-San3, Li, Tony3, Martyn, Calla3, Oliveira, Glenn4, Saraf, Sharada4, Grubaugh, Nathan D.4,5, Andersen, Kristian G.4, Thissen, James6, Allen, Jonathan6, Borucki, Monica6, Tsetsarkin, Konstantin A.7, Pletnev, Alexander G.7 |
| المصدر: |
Journal of Virology. 2020, Vol. 94 Issue 24, p1-20. 20p. |
| مصطلحات موضوعية: |
*RHESUS monkeys, *ZIKA virus infections, *ZIKA virus, *VIRAL mutation, *AEDES aegypti, *MACAQUES, *VIRAL genetics |
| مستخلص: |
Although fetal death is now understood to be a severe outcome of congenital Zika syndrome, the role of viral genetics is still unclear. We sequenced Zika virus (ZIKV) from a rhesus macaque fetus that died after inoculation and identified a single intrahost substitution, M1404I, in the ZIKV polyprotein, located in nonstructural protein 2B (NS2B). Targeted sequencing flanking position 1404 in 9 additional macaque mothers and their fetuses identified M1404I at a subconsensus frequency in the majority (5 of 9, 56%) of animals and some of their fetuses. Despite its repeated presence in pregnant macaques, M1404I has occurred rarely in humans since 2015. Since the primary ZIKV transmission cycle is human-mosquito-human, mutations in one host must be retained in the alternate host to be perpetuated. We hypothesized that ZIKV I1404 increases viral fitness in nonpregnant macaques and pregnant mice but is less efficiently transmitted by vectors, explaining its low frequency in humans during outbreaks. By examining competitive fitness relative to that of ZIKV M1404, we observed that ZIKV I1404 produced lower viremias in nonpregnant macaques and was a weaker competitor in tissues. In pregnant wild-type mice, ZIKV I1404 increased the magnitude and rate of placental infection and conferred fetal infection, in contrast to ZIKV M1404, which was not detected in fetuses. Although infection and dissemination rates were not different, Aedes aegypti mosquitoes transmitted ZIKV I1404 more poorly than ZIKV M1404. Our data highlight the complexity of arbovirus mutation-fitness dynamics and suggest that intrahost ZIKV mutations capable of augmenting fitness in pregnant vertebrates may not necessarily spread efficiently via mosquitoes during epidemics. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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