Year: 2017
Type: article
Abstract: We characterise the evolutionary dynamics of influenza infection described by viral sequence data collected from two challenge studies conducted in human hosts. Viral sequence data were collected at regular intervals from infected hosts. Changes in the sequence data observed across time show that the within-host evolution of the virus was driven by the reversion of variants acquired during previous passaging of the virus. Treatment of some patients with oseltamivir on the first day of infection did not lead to the emergence of drug resistance variants in patients. Using an evolutionary model, we inferred the effective rate of reassortment between viral segments, measuring the extent to which randomly chosen viruses within the host exchange genetic material. We find strong evidence that the rate of effective reassortment is low, such that genetic associations between polymorphic loci in different segments are preserved during the course of an infection in a manner not compatible with epistasis. Combining our evidence with that of previous studies we suggest that spatial heterogeneity in the viral population may reduce the extent to which reassortment is observed. Our results do not contradict previous findings of high rates of viral reassortment in vitro and in small animal studies, but indicate that in human hosts the effective rate of reassortment may be substantially more limited.
Source: PLoS Pathogens
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,698
Funders: National Science Foundation, U.S. Department of Health and Human Services, Wellcome Trust, Duke-NUS Medical School, Royal Society, University of Cambridge, National Institutes of Health, Defense Advanced Research Projects Agency, Advanced Research Projects Agency, Science and Technology Facilities Council, National Institute on Aging, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: G1037014486, G1160089588, G1309323827, G1436341924, Medical Scientist Training Program, G2394953455, G3306888566, The J. Craig Venter Institute Genome Center for Infectious Diseases, G3743703474, G4971250455, Center for Statistics and Quantitative Infectious Diseases, G5341321155, G5368866882, G6360050176, Multi-locus models of pathogen evolution., G7620926480, G7735215634, G7998085565, G8100668736, Multi-locus models of pathogen evolution., G9000211372, Duke Claude D. Pepper Older Americans Independence Center, G921956316
OpenAlex ID: W2586921983