Format

Send to

Choose Destination
PLoS One. 2018 Sep 7;13(9):e0198303. doi: 10.1371/journal.pone.0198303. eCollection 2018.

Extensive recoding of dengue virus type 2 specifically reduces replication in primate cells without gain-of-function in Aedes aegypti mosquitoes.

Author information

1
Stony Brook University, Department of Molecular Genetics and Microbiology, Stony Brook University School of Medicine, Stony Brook, New York, United States of America.
2
Codagenix, Incorporated, Farmingdale, New York, United States of America.
3
Wadsworth Center, New York State Department of Health, Slingerlands, New York, United States of America.
4
School of Public Health, State University of New York at Albany, Rensselaer, New York, United States of America.

Abstract

Dengue virus (DENV), an arthropod-borne ("arbovirus") virus, causes a range of human maladies ranging from self-limiting dengue fever to the life-threatening dengue shock syndrome and proliferates well in two different taxa of the Animal Kingdom, mosquitoes and primates. Mosquitoes and primates show taxonomic group-specific intolerance to certain codon pairs when expressing their genes by translation. This is called "codon pair bias". By necessity, dengue viruses evolved to delicately balance this fundamental difference in their open reading frames (ORFs). We have undone the evolutionarily conserved genomic balance in the DENV2 ORF sequence and specifically shifted the encoding preference away from primates. However, this recoding of DENV2 raised concerns of 'gain-of-function,' namely whether recoding could inadvertently increase fitness for replication in the arthropod vector. Using mosquito cell lines and two strains of Aedes aegypti we did not observe any increase in fitness in DENV2 variants codon pair deoptimized for humans. This ability to disrupt and control DENV2's host preference has great promise towards developing the next generation of synthetic vaccines not only for DENV but for other emerging arboviral pathogens such as chikungunya virus and Zika virus.

PMID:
30192757
PMCID:
PMC6128446
DOI:
10.1371/journal.pone.0198303
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

EW is a co-founder and consultant of Codagenix, Inc., SM and CS are employed by Codagenix, Inc., a commercial company that is developing vaccines based on recoded viruses. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center