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A Zika virus envelope mutation preceding the 2015 epidemic enhances virulence and fitness for transmission
- Source :
- Proc Natl Acad Sci U S A
- Publication Year :
- 2020
- Publisher :
- Proceedings of the National Academy of Sciences, 2020.
-
Abstract
- Arboviruses maintain high mutation rates due to lack of proofreading ability of their viral polymerases, in some cases facilitating adaptive evolution and emergence. Here we show that, just before its 2013 spread to the Americas, Zika virus (ZIKV) underwent an envelope protein V473M substitution (E-V473M) that increased neurovirulence, maternal-to-fetal transmission, and viremia to facilitate urban transmission. A preepidemic Asian ZIKV strain (FSS13025 isolated in Cambodia in 2010) engineered with the V473M substitution significantly increased neurovirulence in neonatal mice and produced higher viral loads in the placenta and fetal heads in pregnant mice. Conversely, an epidemic ZIKV strain (PRVABC59 isolated in Puerto Rico in 2015) engineered with the inverse M473V substitution reversed the pathogenic phenotypes. Although E-V473M did not affect oral infection of Aedes aegypti mosquitoes, competition experiments in cynomolgus macaques showed that this mutation increased its fitness for viremia generation, suggesting adaptive evolution for human viremia and hence transmission. Mechanistically, the V473M mutation, located at the second transmembrane helix of the E protein, enhances virion morphogenesis. Overall, our study revealed E-V473M as a critical determinant for enhanced ZIKV virulence, intrauterine transmission during pregnancy, and viremia to facilitate urban transmission.
- Subjects :
- Male
0301 basic medicine
Mutation rate
030106 microbiology
Virulence
Viremia
Aedes aegypti
medicine.disease_cause
law.invention
Zika virus
Mice
03 medical and health sciences
Viral Envelope Proteins
Pregnancy
law
medicine
Animals
Humans
Epidemics
Phylogeny
Mutation
Multidisciplinary
biology
Zika Virus Infection
virus diseases
Zika Virus
Viral Load
Biological Sciences
medicine.disease
biology.organism_classification
Virology
Mice, Inbred C57BL
Macaca fascicularis
030104 developmental biology
Transmission (mechanics)
Female
Viral load
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 117
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....98c50cc759a388566ed7e5fa3f4c0699