Reassortment between human A(H3N2) viruses is an important evolutionary mechanism

National Reference Centre for Influenza, Robert Koch Institute, Nordufer 20, 13353 Berlin, Germany.
Vaccine (Impact Factor: 3.49). 12/2006; 24(44-46):6683-90. DOI: 10.1016/j.vaccine.2006.05.105
Source: PubMed

ABSTRACT Phylogenetic relationships of whole genomes of H3N2 viruses circulating in Germany during a 6-year period from 1998 to 2005 revealed the co-circulation of different lineages of viruses. Multiple reassortment events occurred during this time between viruses belonging to different lineages or different subgroups. Strains isolated during 1998-1999 were characterised by a surprisingly high heterogeneity and multiple reassortment events. Seventy percent of the examined 1998-1999 viruses had completely different genome compositions. To our knowledge, such an exceptional high proportion of different reassortant strains, encompassing all eight genome segments, have not been described before. In contrast, only one reassortant virus was prevalent during 1999-2000 even though two of the three 1998-1999 lineages were co-circulating. Reassortant viruses were isolated also in each of the other seasons. However, the proportion of H3N2 viruses with different genome compositions varied from season to season. Strains with a reassortant NA played an important role and were also detected during 2003-2004 and 2004-2005 accounting for 45% and 70% of the circulating H3N2 viruses, respectively. Moreover, different reassortment events occurring during these seasons included also the PB1, PB2 and NP genes. The results presented here emphasize that genetic reassortment is an important factor in the evolution of H3N2 viruses and highlight the need for a comprehensive analysis of influenza viruses, especially with regard to the annual vaccine composition.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Influenza A(H3N2) viruses became widespread in humans during the 1968 H3N2 virus pandemic and have been a major cause of influenza epidemics ever since. The viruses evolve continuously by reassortment and genomic evolution. Antigenic drift is the cause for the need to update the influenza vaccine frequently. Using two datasets that span the entire period of circulation of human influenza A(H3N2) viruses, it was shown that the influenza A(H3N2) virus evolution could be mapped into thirteen antigenic clusters. Here, we have analyzed the full genome of 286 influenza A(H3N2) viruses from these two datasets to investigate the genomic evolution and reassortment patterns. Numerous reassortment events, scattered over the entire period of virus circulation, were found, but most prominently in viruses circulating between 1991 and 1998. Some of these reassortment events persisted over time, and one of these coincided with an antigenic cluster transition. Further, selection pressures and nucleotide and amino acid substitution rates of all proteins were studied, including the recently discovered PB1-N40, PA-X, PA-N155, and PA-N182 proteins. Rates of nucleotide and amino acid substitution were most pronounced for hemagglutinin, neuraminidase, and PB1-F2 proteins. Selection pressures were highest in hemagglutinin, neuraminidase, matrix 1 and non-structural protein 1. This study of genotype in relation to the antigenic phenotype throughout the entire period of circulation of human influenza A(H3N2) viruses leads to a better understanding of its evolution.
    Journal of Virology 12/2013; 88(5). DOI:10.1128/JVI.02163-13 · 4.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this work, nineteen influenza A/H3N2 viruses isolated in Mexico between 2003 and 2012 were studied. Our findings show that different human A/H3N2 viral lineages co-circulate within a same season and can also persist locally in between different influenza seasons, increasing the chance for genetic reassortment events. A novel minor cluster was also identified, named here as Korea, that circulated worldwide during 2003. Frequently, phylogenetic characterization did not correlate with the determined antigenic identity, supporting the need for the use of molecular evolutionary tools additionally to antigenic data for the surveillance and characterization of viral diversity during each flu season. This work represents the first long-term molecular epidemiology study of influenza A/H3N2 viruses in Mexico based on the complete genomic sequences and contributes to the monitoring of evolutionary trends of A/H3N2 influenza viruses within North and Central America.
    PLoS ONE 07/2014; 9(7):e102453. DOI:10.1371/journal.pone.0102453 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: One pathway through which pandemic influenza strains might emerge is reassortment from coinfection of different influenza A viruses. Seasonal influenza vaccines are designed to target the circulating strains, which intuitively decreases the prevalence of coinfection and the chance of pandemic emergence due to reassortment. However, individual-based analyses on 2009 pandemic influenza show that the previous seasonal vaccination may increase the risk of pandemic A(H1N1) pdm09 infection. In view of pandemic influenza preparedness, it is essential to understand the overall effect of seasonal vaccination on pandemic emergence via reassortment. In a previous study we applied a population dynamics approach to investigate the effect of infection-induced cross-immunity on reducing such a pandemic risk. Here the model was extended by incorporating vaccination for seasonal influenza to assess its potential role on the pandemic emergence via reassortment and its effect in protecting humans if a pandemic does emerge. The vaccination is assumed to protect against the target strains but only partially against other strains. We find that a universal seasonal vaccine that provides full-spectrum cross-immunity substantially reduces the opportunity of pandemic emergence. However, our results show that such effectiveness depends on the strength of infection-induced cross-immunity against any novel reassortant strain. If it is weak, the vaccine that induces cross-immunity strongly against non-target resident strains but weakly against novel reassortant strains, can further depress the pandemic emergence; if it is very strong, the same kind of vaccine increases the probability of pandemic emergence. Two types of vaccines are available: inactivated and live attenuated, only live attenuated vaccines can induce heterosubtypic immunity. Current vaccines are effective in controlling circulating strains; they cannot always help restrain pandemic emergence because of the uncertainty of the oncoming reassortant strains, however. This urges the development of universal vaccines for prevention of pandemic influenza.
    PLoS ONE 12/2014; 9(12):e114637. DOI:10.1371/journal.pone.0114637 · 3.53 Impact Factor