J.I.D.: Dynamic Variation & Reversion in the Signature Amino Acids of H7N9 Virus During Human Infection

[Michael Coston]

J.I.D.: Dynamic Variation & Reversion in the Signature Amino Acids of H7N9 Virus During Human Infection


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#13,288


Like all organisms, flu viruses must constantly adapt in order to survive in new surroundings. While well adapted to avian hosts, bird flu viruses (like H7N9, H5N1, H5N6) can occasionally jump to humans (and other mammals), whose physiology can present barriers to its spread and survival.

But flu viruses have a secret weapon.​

As they replicate in a host, they generate millions of copies in a few short hours. Since flu viruses are notoriously sloppy replicators, they make numerousmistakes. Most of these faulty copies are evolutionary failures and fall by the wayside, but occasionally a new mutation will appear that is better suited to the new host.

Host adapted viruses are more likely to replicate and survive, and over time, can become dominant and even `fixed' in the virus.​

As long as humans remain a dead end host (i.e. they don't transmit efficiently to other humans) for avian flu, the biggest danger is to the health of the infected individual. But should these viruses gain the ability to transmit efficiently, then the real problems begin.

While we often see reports of `mammalian adaptations' in H7N9, or mutations that favor anti-viral resistance, our understanding of exactly when (and where) these mutations are spawned is still lacking.​

Adding to our knowledge today, we've a new, open access study, published in the Journal of Infectious Diseases, which looks at the evolution of H7N9in 11 subjects during the course of their infection. Today's report focuses on 3 mutations we've seen often in the past;

• NA R292K which can provide resistance not only to oseltamivir, but to zanamivir and peramivir as well(see EID Journal: R292K Substitution & Antiviral Resistance)
• PB2 E627K which enables an influenza virus to replicate at the lower temperatures (roughly 33C) normally found in the upper human respiratory tract (see Eurosurveillance: Genetic Analysis Of Novel H7N9 Virus)
• and PB2 D701N (see Dual E627K and D701N mutations in the PB2 protein of A(H7N9) influenza virus increased its virulence in mammalian models)

Due to it length and complexity, I'll simply post the abstract. So you'll want to follow the link to read it in its entirety.

Dynamic Variation and Reversion in the Signature Amino Acids of H7N9 Virus During Human Infection

Xiaohui Zou Qiang Guo Wei Zhang Hui Chen Wei Bai Binghuai Lu Wang Zhang Yanyan Fan Chao Liu Yeming Wang ... Show more

The Journal of Infectious Diseases, jiy217, https://doi.org/10.1093/infdis/jiy217

Published: 24 April 2018 OPEN ACCESS PDF ​

Abstract

Background

Signature amino acids of H7N9 influenza virus play critical roles in human adaption and pathogenesis, but their dynamic variation is unknown during disease development.

Methods

We sequentially collected respiratory samples from H7N9 patients at different timepoints and applied next-generation sequencing (NGS) to the whole genome of the H7N9 virus to investigate the variation at signature sites.​

Results

A total of 11 patients were involved and from whom 29 samples were successfully sequenced, including samples from multiple timepoints in 9 patients. NA R292K, PB2 E627K, and D701N were the three most dynamic mutations. The oseltamivir resistance-related NA R292K mutation was present in 9 samples from 5 patients, including one sample obtained before antiviral therapy.​

In all patients with the NA 292K mutation, the oseltamivir-sensitive 292R genotype persisted and was not eliminated by antiviral treatment. The PB2 E627K substitution was present in 18 samples from 8 patients, among which 12 samples demonstrated a mixture of E/K and the 627K frequency exhibited dynamic variation. Dual D701N and E627K mutations emerged but failed to achieve predominance in any of the samples.​

Conclusions

Signature amino acids in PB2 and NA demonstrated high polymorphism and dynamic variation within individual patients during H7N9 virus infection.


http://afludiary.blogspot.com/2018/0...ersion-in.html
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[bertrand789]

Merci,

je trouve ?trange de ne rien lire sur le creusot que repr?sente l'?le de Cuba . Ce me semble un vrai carrefour de x migrations, mais on sait quoi de ce qui s'y passe au niveau influenza aviaire, etc ?