Abstract
Evolution of Avian Influenza (AI) viruses – especially of the Highly Pathogenic Avian Influenza (HPAI) H5N1 subtype – is a major issue for the poultry industry. HPAI H5N1 epidemics are associated with huge economic losses and are sometimes connected to human morbidity and mortality. Vaccination (either as a preventive measure or as a means to control outbreaks) is an approach that splits the scientific community, due to the risk of it being a potential driving force in HPAI evolution through the selection of mutants able to escape vaccination-induced immunity. It is therefore essential to study how mutations are selected due to immune pressure. To this effect, we performed an in vitro selection of mutants from HPAI A/turkey/Turkey/1/05 (H5N1), using immune pressure from homologous polyclonal sera. After 42 rounds of selection, we identified 5 amino acid substitutions in the Haemagglutinin (HA) protein, most of which were located in areas of antigenic importance and suspected to be prone to selection pressure. We report that most of the mutations took place early in the selection process. Finally, our antigenic cartography studies showed that the antigenic distance between the selected isolates and their parent strain increased with passage number.
Highlights
Influenza A viruses belong to the family of orthomyxoviridae
The most important outcomes of antigenic drift may be an increased ability of the virus to avoid natural or acquired hostimmunity, as well as a possibility of breaching host-range barriers [6,7,8]. Both the HA and the NA proteins are involved in the process of antigenic drift with the HA implicated much more, since it is the main target of neutralising antibodies and is known to accumulate many point mutations in its epitope or antibodybinding regions [9,10,11,12,13]
We aim to study the evolution of Avian Influenza (AI) viruses by repeated in vitro exposure to targeted pressure from polyclonal immune sera directed against the HA of Highly Pathogenic Avian Influenza (HPAI) H5N1 A/turkey/ Turkey/1/2005
Summary
Influenza A viruses belong to the family of orthomyxoviridae. They are negative single-stranded RNA viruses with a segmented genome that comprises 8 genes. The most important outcomes of antigenic drift may be an increased ability of the virus to avoid natural or acquired hostimmunity, as well as a possibility of breaching host-range barriers [6,7,8]. Both the HA and the NA proteins are involved in the process of antigenic drift with the HA implicated much more, since it is the main target of neutralising antibodies and is known to accumulate many point mutations in its epitope or antibodybinding regions [9,10,11,12,13]
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