JVI: Analysis by single gene reassortment demonstrates that the 1918 influenza virus is functionally compatible with a low pathogenicity avian influen

[tetano]

Published ahead of print 20 June 2012, doi: 10.1128/​JVI.00887-12

Analysis by single gene reassortment demonstrates that the 1918 influenza virus is functionally compatible with a low pathogenicity avian influenza virus in mice.

Li Qi,
A. Sally Davis,
Brett W. Jagger,
Louis M. Schwartzman,
Eleca J. Dunham,
John C. Kash and
Jeffery K. Taubenberger#

Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

ABSTRACT

The 1918-1919 ?Spanish? influenza pandemic is estimated to have caused 50 million deaths worldwide. Understanding the origin, virulence, and pathogenic properties of past pandemic influenza viruses, including the 1918 virus, is crucial for current public health preparedness and future pandemic planning. The origin of the 1918 pandemic virus has not been resolved but its coding sequences are very avian influenza-like. The proteins encoded by the 1918 virus differ from typical low pathogenicity avian influenza viruses at only a small number of amino acids in each open reading frame. In this study, a series of chimeric 1918 influenza viruses were created in which each of the eight 1918 gene segments was replaced individually with the corresponding gene segment of a prototypical low pathogenicity avian influenza (LPAI) H1N1 virus in order to investigate functional compatibility of the 1918 virus genome with gene segments from an LPAI virus and to identify gene segments and mutations important for mammalian adaptation. This set of eight ?7:1? chimeric viruses was compared to the parental 1918 and LPAI H1N1 viruses in intransally infected mice. Seven of the 1918:LPAI 7:1 chimeric viruses replicated and caused disease equivalent to the fully reconstructed 1918 virus. Only the chimeric 1918 virus containing the avian influenza PB2 gene segment was attenuated in mice. This attenuation could be corrected by the single E627K amino acid change, further confirming the importance of this change in mammalian adaptation and mouse pathogenicity. While the mechanisms of influenza virus host switch, and particularly mammalian host adaptation are still only partly understood, these data suggest that the 1918 virus, whatever its origin, is very avian-influenza like.


http://jvi.asm.org/content/early/2012/06/14/JVI.00887-12.abstract

 

[gsgs]

Re: JVI: Analysis by single gene reassortment d...

Re: JVI: Analysis by single gene reassortment d...

http://jvi.asm.org/content/86/17/9211.full

maybe the first wave was just 1918(AI-PB2) ??!?!?

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Compared to the 1918 parental virus, a mutant isogenic 1918
virus (1918PB2-E627) with the single 1918 PB2 change of K627E
(back to the avian influenza consensus codon), was markedly at-
tenuated in mice, causing neither appreciable weight loss (Fig. 3)
nor mortality

To assess whether the PB2 codon 627
might have been under selection pressure to mutate during the
1918AI-PB2 infection in mice, the PB2 gene was amplified and se-
quenced by reverse transcription-PCR (RT-PCR) from RNA iso-
lated from 25 individual plaques derived from culture of a mouse
lung at dpi 5. As has been reported in other systems (5), K627
revertants were observed in 23 of 25 plaques (92%) from the
1918AI-PB2(E627) virus-infected mouse lung. In 3 of the 23
plaques with PB2 K627, another coding change, D611N, was also
observed.

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when we assume that this is similar in humans and that
1918(627E) behaves the same way, then the acquisition
of 627K in human lungs may still mean that in transmissions
of 627E infected people 627E is usually still transmitted,
even late in the disease, since transmission occurs from the
upper respiratory tract and not the lungs.

But by that theory, then in the 2nd wave (1918) and 1918-627E
would have co-existed and (1918) was more successful and
replaced first-wave-1918-627E.

Well, it's unexpected that the first wave virus had been so suddenly
and completely replaced when they had been so similar, with same antigenics.
And why it took so long - several months - until this occurred.

Maybe 627K together with 225G(4) was needed
oh dear, hopefully that's not the pattern for pH1N1

the virus AI-627K would have been interesting
so to see, whether such an event may occur again in future
just with a virus close to the mallard-index=avian consensus in the inner segments

> Therefore, at least in the context of
> the other seven 1918 genes, a low-pathogenicity avian HA could
> elicit responses similar to the 1918 HA protein.


interesting would also be also throat swabs
and then transmission in ferrets 1918-AI-PB2 , AI-627K ,
1918-AI-HA
maybe they did it already but don't dare to publish ...