Evolution of H3N2 Influenza Virus in a Guinea Pig Model

Abstract

Studies of influenza virus evolution under controlled experimental conditions can provide a better understanding of the consequences of evolutionary processes with and without immunological pressure. Characterization of evolved strains assists in the development of predictive algorithms for both the selection of subtypes represented in the seasonal influenza vaccine and the design of novel immune refocused vaccines. To obtain data on the evolution of influenza in a controlled setting, naïve and immunized Guinea pigs were infected with influenza A/Wyoming/2003 (H3N2). Virus progeny from nasal wash samples were assessed for variation in the dominant and other epitopes by sequencing the hemagglutinin (HA) gene to quantify evolutionary changes. Viral RNA from the nasal washes from infection of naïve and immune animals contained 6% and 24.5% HA variant sequences, respectively. Analysis of mutations relative to antigenic epitopes indicated that adaptive immunity played a key role in virus evolution. HA mutations in immunized animals were associated with loss of glycosylation and changes in charge and hydrophobicity in and near residues within known epitopes. Four regions of HA-1 (75–85, 125–135, 165–170, 225–230) contained residues of highest variability. These sites are adjacent to or within known epitopes and appear to play an important role in antigenic variation. Recognition of the role of these sites during evolution will lead to a better understanding of the nature of evolution which help in the prediction of future strains for selection of seasonal vaccines and the design of novel vaccines intended to stimulated broadened cross-reactive protection to conserved sites outside of dominant epitopes.

Genetic diversity of influenza A(H3N2) viruses in Northern Cameroon during the 2014‐2016 influenza seasons

“…Glycosylation and deglycosylation are essential viral mechanisms to accommodate in the host organisms . There was no distinct glycosylation pattern observed across influenza seasons in Northern Cameroon.…”

Reassortment Complements Spontaneous Mutation in Influenza A Virus NP and M1 Genes To Accelerate Adaptation to a New Host

“…In either case, the transmission of diversity may allow variants with moderate fitness advantages to emerge and grow out over the course of multiple transmission events. Preexisting immunity in guinea pigs has been shown to impact virus evolution during the course of a single infection (39), which raises the possibility of modeling in GPs viral evolution during transmission to animals with various states of preexisting immunity, as has been demonstrated in swine, horses, and dogs (36,37,40).…”

Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model

“…A(H1N1), A(H3N8) and A(H3N2) viruses have been passaged multiple times through immunized mice [13] and once through dogs [14] and guinea pigs [17], respectively. A(H1N1)pdm09 virus has been cultured in embryonated hen's eggs in the presence of mouse monoclonal antibodies [16] or in MDCK cells in the presence of a human monoclonal antibody [15].…”