J Virol. Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission.

[Giuseppe]

Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission. (J Virol., abstract, edited)

5. J Virol. 2010 Feb 3. [Epub ahead of print]

Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission.

Herfst S, Chutinimitkul S, Ye J, de Wit E, Munster VJ, Schrauwen EJ, Bestebroer TM, Jonges M, Meijer A, Koopmans M, Rimmelzwaan GF, Osterhaus AD, Perez DR, Fouchier RA. - National Influenza Center and Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Veterinary Medicine, University of Maryland, College Park, Maryland, United States of America; and National Institute for Public Health and the Environment, Laboratory for Infectious Diseases and Screening, Bilthoven, The Netherlands.

In the first six months of the H1N1 swine-origin influenza virus (S-OIV) pandemic, the vast majority of infections were relatively mild. It has been postulated that mutations in the viral genome could result in more virulent viruses, leading to a more severe pandemic. Mutations E627K and D701N in the PB2 protein have previously been identified as determinants of avian and pandemic influenza virus virulence in mammals. These mutations were absent in S-OIVs detected early in the 2009 pandemic. Here, using reverse genetics, mutations E627K, D701N and E677G were introduced in the prototype S-OIV A/Netherlands/602/2009, and their effect on virus replication, virulence, and transmission was investigated. Mutations E627K and D701N caused increased reporter gene expression driven by the S-OIV polymerase complex. None of the three mutations affected virus replication in vitro. The mutations had no major impact on virus replication in the respiratory tracts of mice and ferrets or on pathogenesis. All three mutant viruses were transmitted via aerosols or respiratory droplets in ferrets. Thus, the impact of key known virulence markers in PB2 in the context of current S-OIVs was surprisingly small. This study does not exclude the possibility of emergence of S-OIVs with other virulence-associated mutations in the future. We conclude that surveillance studies aimed to detect S-OIVs with increased virulence or transmission should not rely solely on virulence markers identified in the past, but should include detailed characterization of virus phenotypes, guided by genetic signatures of viruses detected in severe cases of disease in humans.

PMID: 20130063 [PubMed - as supplied by publisher]
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[gsgs]

Re: J Virol. Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission.

all our previous excitement invain

[avexflow]

Re: J Virol. Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission.

no surprise for me, as you may notice, the PB2 627K does not totally confer the pathogenicity of disease in human, and even most of them were PB2 627E

what I mean is, doing experiment in animal is one thing, but the real situation in human is always omitted, just like 627K is commonly found in seasonal flu, but it does not cause significant disease severity, I believe there are several more points mutation that is mutually affecting each others and conferring the pathogenicity. certainly deeper investigation has to be done to further address this question

[Sally Furniss]

Re: J Virol. Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission.

Welcome avexflow and thank you!

[mixin]

Re: J Virol. Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission.

Welcome to the forum, avexflow.

I believe there are several more points mutation that is mutually affecting each others and conferring the pathogenicity.

I'm interested in hearing your opinion on which ones these are and why.

[sharon sanders]

Re: J Virol. Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission.

Welcome Avexflow!

[avexflow]

Re: J Virol. Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission.

first of all, i must thank for all the warm welcomes and really nice for me to be here.

Why I said 627K is not the sole significant mutation in "human" is because when you challenge avian species (particularly chicken or some susceptible species), you will found no difference at all, in terms of survival time or disease pathology.

However, when we talk about that in human, even the killing strain is not all 627K, and when you do the alignment, most are them are purely E and suggesting that the direct transmission of the viruses from poultry to human.

So, we have a better understanding that, E/K does not really confer the pathogenecity in human, do not forget most of the studies were done with mice, so people will say "mammals", and I think this point have to clarify. I have few studied before and I did see the huge differences between E and K in mice by using reverse genetics.

So, answering my previous point, why I said several other mutations also do the job? When you look into the literatures, you will start to see the mutation out of 627 and more likely to compensate the virulence or the transmission of the virus (Andrew Mehlea and Jennifer A. Doudnaa PNAS).

I would say, I will believe this model (compensation, 1 to 1, or several mutations within the RNPs) rather than just one particular mutation could confer the disease severity.

Welcome to the forum, avexflow.
I'm interested in hearing your opinion on which ones these are and why.