Phylodynamic Analysis of the Emergence and Epidemiological Impact of Transmissible Defective Dengue Viruses

PLoS Pathogens

Ruian Ke¹  James O. Lloyd-Smith²  John Aaskov³  Edward C. Holmes⁴ 

[1] Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California, United States of America;Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America;Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia;School of Biological Sciences and Sydney Medical School, The University of Sydney, Sydney, Australia

关键词: Dengue virus;    Viral transmission;    infection;    Phylogenetic analysis;    Mosquitoes;    Myanmar;    Viral pathogens;    Evolutionary emergence;    Viral evolution;   

DOI  :  10.1371/journal.ppat.1003193

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Intra-host sequence data from RNA viruses have revealed the ubiquity of defective viruses in natural viral populations, sometimes at surprisingly high frequency. Although defective viruses have long been known to laboratory virologists, their relevance in clinical and epidemiological settings has not been established. The discovery of long-term transmission of a defective lineage of dengue virus type 1 (DENV-1) in Myanmar, first seen in 2001, raised important questions about the emergence of transmissible defective viruses and their role in viral epidemiology. By combining phylogenetic analyses and dynamical modeling, we investigate how evolutionary and ecological processes at the intra-host and inter-host scales shaped the emergence and spread of the defective DENV-1 lineage. We show that this lineage of defective viruses emerged between June 1998 and February 2001, and that the defective virus was transmitted primarily through co-transmission with the functional virus to uninfected individuals. We provide evidence that, surprisingly, this co-transmission route has a higher transmission potential than transmission of functional dengue viruses alone. Consequently, we predict that the defective lineage should increase overall incidence of dengue infection, which could account for the historically high dengue incidence reported in Myanmar in 2001–2002. Our results show the unappreciated potential for defective viruses to impact the epidemiology of human pathogens, possibly by modifying the virulence-transmissibility trade-off, or to emerge as circulating infections in their own right. They also demonstrate that interactions between viral variants, such as complementation, can open new pathways to viral emergence.

【 授权许可】

CC BY