Abstract
Avian influenza viruses present an emerging epidemiological concern as some strains of H5N1 avian influenza can cause severe infections in humans with lethality rates of up to 60%. These have been in circulation since 1997 and recently a novel H7N9-subtyped virus has been causing epizootics in China with lethality rates around 20%. To better understand the replication kinetics of these viruses, we combined several extensive viral kinetics experiments with mathematical modelling of in vitro infections in human A549 cells. We extracted fundamental replication parameters revealing that, while both the H5N1 and H7N9 viruses replicate faster and to higher titers than two low-pathogenicity H1N1 strains, they accomplish this via different mechanisms. While the H7N9 virions exhibit a faster rate of infection, the H5N1 virions are produced at a higher rate. Of the two H1N1 strains studied, the 2009 pandemic H1N1 strain exhibits the longest eclipse phase, possibly indicative of a less effective neuraminidase activity, but causes infection more rapidly than the seasonal strain. This explains, in part, the pandemic strain’s generally slower growth kinetics and permissiveness to accept mutations causing neuraminidase inhibitor resistance without significant loss in fitness. Our results highlight differential growth properties of H1N1, H5N1 and H7N9 influenza viruses.
Highlights
Avian influenza viruses present an emerging epidemiological concern as some strains of H5N1 avian influenza can cause severe infections in humans with lethality rates of up to 60%
The results provide a detailed quantification of the replication parameters characterizing influenza infections with seasonal H1N1, 2009 pandemic H1N1, low pathogenicity avian influenza (LPAI) H7N9 and highly pathogenic avian influenza (HPAI) H5N1 viruses, and highlight the distinct differences in their replicative strategies, despite the fact that they all adhere to the same basic processes for replication
We evaluated and compared the infection kinetics of two strains of human influenza A H1N1 causing relatively mild disease in humans, a seasonal A/New Caledonia/20/1999-like clinical isolate and the 2009 pandemic H1N1 strain A/Mexico/INDRE4487/2009, as well as two viruses causing severe human infections, the HPAI H5N1 strain A/Indonesia/05/2005 and the LPAI H7N9 strain A/Anhui/1/2013
Summary
Avian influenza viruses present an emerging epidemiological concern as some strains of H5N1 avian influenza can cause severe infections in humans with lethality rates of up to 60%. Most prominent is the highly pathogenic avian influenza (HPAI) H5N1 subtype virus that was first identified in human cases of infection in 199712 Since this subtype has been in circulation in migratory birds and has caused large-scale poultry outbreaks in Asia, Europe and Africa as well as infection in nearly 700 human cases with about 60% lethality[11]. A great deal of investigation has been dedicated to the identification and delineation of the role of viral determinants of pathogenicity and adaptation of virus to new hosts following zoonotic transmission of viruses, including, for example, the identification of HA as the major virulence determinant in 1918 H1N1 Spanish influenza strain[20] or the aerosol transmission of H5N1 HPAI in ferrets[21,22] The consequences of these viral determinants of pathogenicity are frequently characterized by comparison of viruses containing these determinants with low virulence variants in animal models and by in vitro growth kinetics (e.g.23–31). Most methods characterize discrete properties or activities of viral proteins or define the properties of a virus by readouts, such as virus yield in vitro or disease outcome in vivo, without providing any information regarding the dynamics of interaction between a virus and its host cell
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