Evolution of an Eurasian Avian-like Influenza Virus in Naïve and Vaccinated Pigs

PLoS Pathogens

Gregory J. Baillie¹  Jennifer A. Mumford¹  Mario Caccamo²  Pablo R. Murcia²  Lucy Lloyd²  James L. N. Wood³  Edward C. Holmes⁴  Joseph Hughes⁵  Patrizia Battista⁵  Paul Kellam⁶  Doug Ormond⁶  Ricardo H. Ramirez-Gonzalez⁷  Karen Oliver⁷  Bryan T. Grenfell⁷  Debra Elton⁷ 

[1] Animal Health Trust, Centre for Preventive Medicine, Lanwades Park, Newmarket, United Kingdom;Cambridge Infectious Diseases Consortium, Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom;Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, Pennsylvania, United States of America;Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America;Medical Research Council-University of Glasgow Centre for Virus Research, Institute of Infection, Inflammation and Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom;The Genome Analysis Centre, Norwich Research Park, Norwich, United Kingdom;Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom

关键词: Swine;    Microbial mutation;    Influenza viruses;    Viral evolution;    Mutation detection;    Evolutionary genetics;    Evolutionary immunology;    Influenza;   

DOI  :  10.1371/journal.ppat.1002730

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Influenza viruses are characterized by an ability to cross species boundaries and evade host immunity, sometimes with devastating consequences. The 2009 pandemic of H1N1 influenza A virus highlights the importance of pigs in influenza emergence, particularly as intermediate hosts by which avian viruses adapt to mammals before emerging in humans. Although segment reassortment has commonly been associated with influenza emergence, an expanded host-range is also likely to be associated with the accumulation of specific beneficial point mutations. To better understand the mechanisms that shape the genetic diversity of avian-like viruses in pigs, we studied the evolutionary dynamics of an Eurasian Avian-like swine influenza virus (EA-SIV) in naïve and vaccinated pigs linked by natural transmission. We analyzed multiple clones of the hemagglutinin 1 (HA1) gene derived from consecutive daily viral populations. Strikingly, we observed both transient and fixed changes in the consensus sequence along the transmission chain. Hence, the mutational spectrum of intra-host EA-SIV populations is highly dynamic and allele fixation can occur with extreme rapidity. In addition, mutations that could potentially alter host-range and antigenicity were transmitted between animals and mixed infections were commonplace, even in vaccinated pigs. Finally, we repeatedly detected distinct stop codons in virus samples from co-housed pigs, suggesting that they persisted within hosts and were transmitted among them. This implies that mutations that reduce viral fitness in one host, but which could lead to fitness benefits in a novel host, can circulate at low frequencies.

【 授权许可】

CC BY