NS1 codon usage adaptation to humans in pandemic Zika virus

Abstract

BACKGROUND Zika virus (ZIKV) was recognised as a zoonotic pathogen in Africa and southeastern Asia. Human infections were infrequently reported until 2007, when the first known epidemic occurred in Micronesia. After 2013, the Asian lineage of ZIKV spread along the Pacific Islands and Americas, causing severe outbreaks with millions of human infections. The recent human infections of ZIKV were also associated with severe complications, such as an increase in cases of Guillain-Barre syndrome and the emergence of congenital Zika syndrome.OBJECTIVES To better understand the recent and rapid expansion of ZIKV, as well as the presentation of novel complications, we compared the genetic differences between the African sylvatic lineage and the Asian epidemic lineage that caused the recent massive outbreaks.FINDINGS The epidemic lineages have significant codon adaptation in NS1 gene to translate these proteins in human and Aedes aegypti mosquito cells compared to the African zoonotic lineage. Accordingly, a Brazilian epidemic isolate (ZBR) produced more NS1 protein than the MR766 African lineage (ZAF) did, as indicated by proteomic data from infections of neuron progenitor cells-derived neurospheres. Although ZBR replicated more efficiently in these cells, the differences observed in the stoichiometry of ZIKV proteins were not exclusively explained by the differences in viral replication between the lineages.MAIN CONCLUSIONS Our findings suggest that natural, silent translational selection in the second half of 20th century could have improved the fitness of Asian ZIKV lineage in human and mosquito cells.

Emerging infectious diseases in Africa in the 21st century

“…The link between Zika virus and severe malformations of the central nervous system (particularly microcephaly) has been demonstrated by many studies in Brazil and has been reported retrospectively in French Polynesia [48] . Genetic differences between African and Asian/American strains of Zika virus and appearance of the ‘pathogenic clone’ may explain the emergence of Zika virus infections in South America and Asia [48] , [49] .

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Biological Characteristics and Patterns of Codon Usage Evolution for the African Genotype Zika Virus

“…The abrupt variation observed in ZIKV population sizes over time could be correlated to the rapid increase of available sequencing data [ 64 ] and to the recent wide distribution of ZIKV from the Pacific Islands to the Americas [ 30 , 31 , 32 , 33 ]. The high NS1 CAI values of the Asian genotype for the human genome confirmed in this study were associated with the Asian genotype ZIKV for humans [ 65 ].…”

“…This clearly shows that the African genotype ZIKV also has the potential to efficiently replicate in humans. This is particularly true for the CAI for the E and NS5 proteins [ 65 ], which have a major role in flaviviruses replication and virulence [ 17 ].…”

Genetic Adaptations, Biases, and Evolutionary Analysis of Canine Distemper Virus Asia-4 Lineage in a Fatal Outbreak of Wild-Caught Civets in Thailand

“…Mutation pressure, the external environment, selective transcription, and natural selection are listed as factors that determine codon usage bias. As with other RNA viruses [58][59][60][61], CDV depends on the host susceptibility with respect to survival and transmission. Thus, the CDV codon usage pattern may interact with the virus' ability to infect, adapt, and escape from the host immune responses.…”