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| Influenza Binding - Credit NIAID |
#11,591
Unlike in mammals, where influenza viruses generally produce a respiratory infection, influenza in birds is predominantly a gastrointestinal malady. The virus attaches to - and replicates in – the avian gut, and is spread mostly via infected droppings.
As you might imagine, avian flu viruses are well adapted to attack the kind of cells commonly found within the avian intestinal tract; α2,3-linked sialic acid avian receptor cells.Humans, and many (but not all) mammals have very few α2,3 receptor cells in their upper airway (but do have some deep in the lungs), making it difficult for avian flu viruses to easily attach to, and infect, non-avian species.
Instead, human (or mammalian) adapted flu viruses bind preferentially to α2,6 receptor cells, which are abundant in their upper respiratory systems. Mammalian viruses are also adapted to replicate in the 5 to 10 degree cooler environment of the upper airway, compared to the intestinal tract of birds.
For an avian influenza virus to successfully jump to mammals, it must therefore acquire some very specific mammalian adaptations. Some that we know about, and others we probably don't.
So we watch avian viruses closely for signs they are picking up the types of amino acid changes that could make them more `humanized', and therefore a greater public health threat.
In recent years we've seen a growing diversity in LPAI H9N2 viruses across Asia and the Middle East, and at the same time, a marked increase in the number of human infections reported (see Yunnan Province Reports An H9N2 Infection).
Whether this sudden increase is due to better testing and reporting (a distinct possibility), or due to a change in the virus (also possible), is unknown.
All of which brings us to a new study, recently published in the Journal of Virology, that finds an unexpected mutation (190V in HA) in genotype B69 - the most common genotype circulating in China - aids in the binding affinity to human-type receptors, and enhances replication in mice.
First a link, and the abstract, then I'll return with a bit more.
A Single Mutation at Position 190 in Hemagglutinin Enhances Binding Affinity for Human Type Sialic Acid Receptor and Replication of H9N2 Avian Influenza Virus in Mice.
Abstract
H9N2 avian influenza virus (AIV) has an extended host range but the molecular basis underlying H9N2 AIV transmission to mammals remains unclear.
We isolated more than 900 H9N2 AIVs in our 3-year surveillance in live bird markets in China from 2009 to 2012. Thirty-seven representative isolates were selected for further detailed characterization. These isolates were categorized into 8 genotypes (B64-B71), and formed a distinct antigenic subgroup.
Three isolates belonging to the genotype B69, which is a predominant genotype circulating in China, replicated efficiently in mice, while the viruses in parallel tested in other genotypes replicated poorly although they have a same leucine at position 226 in the hemagglutinin (HA) receptor binding site critical for binding human-like sialic acid receptors as these three viruses.
Further molecular and single mutation analysis revealed that a valine (V) residue at position 190 in HA is responsible for efficient replication of these H9N2 viruses in mice. The 190V in HA does not affect virus receptor binding specificity, but enhances binding affinity to human cells and lung tissues from mouse and human.
All these data indicate that the 190V in HA is one of the important determinants for H9N2 AIVs to cross species barrier to infect mammals despite multiple genes conferring adaptation and replication of H9N2 viruses in mammals. Our findings provide novel insight on understanding host range expansion of H9N2 AIVs.
As we've discussed previously (see here, here, and here), the common denominator between nearly all of the avian viruses (including H5N1, H5N6, H10N8 and LPAI H7N9) that have emerged from China in recent years is that their internal genes can be traced back to the ubiquitous LPAI H9N2 virus.
While H9N2 produces relatively mild illness on its own accord, when it reassorts with H5 or H7 subtypes, it has the ability to produce formidable flu strains.
Over the past 5 years we've also growing seen evidence of its own evolution, including last July in J. Virol: PA Mutation K356R in Avian H9N2 Increases Mammalian Replication & Pathogenicity.
Whether as a standalone viral threat, or in aiding and abetting another avian subtype, the H9N2 virus remains a major player among avian flu viruses, and so we watch its evolution closely.
