Intrahost Genetic Diversity of Dengue Virus in Human Hosts and Mosquito Vectors under Natural Conditions Which Impact Replicative Fitness In Vitro
Issued Date
2023-04-01
Resource Type
eISSN
19994915
Scopus ID
2-s2.0-85156224254
Pubmed ID
37112962
Journal Title
Viruses
Volume
15
Issue
4
Rights Holder(s)
SCOPUS
Bibliographic Citation
Viruses Vol.15 No.4 (2023)
Suggested Citation
Nonyong P., Ekalaksananan T., Phanthanawiboon S., Overgaard H.J., Alexander N., Thaewnongiew K., Sawaswong V., Nimsamer P., Payungporn S., Phadungsombat J., Nakayama E.E., Shioda T., Pientong C. Intrahost Genetic Diversity of Dengue Virus in Human Hosts and Mosquito Vectors under Natural Conditions Which Impact Replicative Fitness In Vitro. Viruses Vol.15 No.4 (2023). doi:10.3390/v15040982 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/82662
Title
Intrahost Genetic Diversity of Dengue Virus in Human Hosts and Mosquito Vectors under Natural Conditions Which Impact Replicative Fitness In Vitro
Author's Affiliation
Faculty of Tropical Medicine, Mahidol University
Chulalongkorn University
Faculty of Medicine, Khon Kaen University
Research Institute for Microbial Diseases
Khon Kaen University
Medical Research Council
Thailand Ministry of Public Health
Norges Miljø- og Biovitenskapelige Universitet
Faculty of Medicine, Chulalongkorn University
Chulalongkorn University
Faculty of Medicine, Khon Kaen University
Research Institute for Microbial Diseases
Khon Kaen University
Medical Research Council
Thailand Ministry of Public Health
Norges Miljø- og Biovitenskapelige Universitet
Faculty of Medicine, Chulalongkorn University
Other Contributor(s)
Abstract
Dengue virus (DENV) is an arbovirus whose transmission cycle involves disparate hosts: humans and mosquitoes. The error-prone nature of viral RNA replication drives the high mutation rates, and the consequently high genetic diversity affects viral fitness over this transmission cycle. A few studies have been performed to investigate the intrahost genetic diversity between hosts, although their mosquito infections were performed artificially in the laboratory setting. Here, we performed whole-genome deep sequencing of DENV-1 (n = 11) and DENV-4 (n = 13) derived from clinical samples and field-caught mosquitoes from the houses of naturally infected patients, in order to analyze the intrahost genetic diversity of DENV between host types. Prominent differences in DENV intrahost diversity were observed in the viral population structure between DENV-1 and DENV-4, which appear to be associated with differing selection pressures. Interestingly, three single amino acid substitutions in the NS2A (K81R), NS3 (K107R), and NS5 (I563V) proteins in DENV-4 appear to be specifically acquired during infection in Ae. aegypti mosquitoes. Our in vitro study shows that the NS2A (K81R) mutant replicates similarly to the wild-type infectious clone-derived virus, while the NS3 (K107R), and NS5 (I563V) mutants have prolonged replication kinetics in the early phase in both Vero and C6/36 cells. These findings suggest that DENV is subjected to selection pressure in both mosquito and human hosts. The NS3 and NS5 genes may be specific targets of diversifying selection that play essential roles in early processing, RNA replication, and infectious particle production, and they are potentially adaptive at the population level during host switching.