Avian influenza H7N7 virus outbreak: Lessons for H7N9

18 April 2013

Influenza H7 diversityAn outbreak of high-pathogenicity avian influenza H7N7 virus that took place on 255 poultry farms in the Netherlands during 2003 has been used to provide clues about the current avian influenza H7N9 viruses in China. During the Dutch outbreak 453 humans showed symptoms of illness and 89 were confirmed to have infection with the virus. Some interesting observations from that outbreak:

  • Conjunctivitis (inflammation of the membranes surrounding the eyelids) was observed in many of the human cases, as well as in later human infections with H7 influenza viruses. Apparently these viruses replicate well in the eye, which bears alpha-2,3 sialic acid receptors. From there the viruses could reach the nasal cavity via the nasolacrimal duct. 
  • There was one fatal infection during the Dutch outbreak, and virus isolated from this individual contained the amino acid change E627K in viral protein PB2, which is associated with higher replication of avian influenza viruses in mammals. This change likely arose during replication of virus in the patient as it was not observed in other isolates. The recent H7N9 isolates from China all have the PB2 E627K mutation.
  • In the Dutch outbreak there was no evidence for human to human transmission of H7N7 viruses. This conclusion is in part supported by phylogenetic analysis of viral sequences, which showed that during the outbreak the viruses diversified into multiple lineages with human strains at the ends of the trees (Figure; click to enlarge. Credit: Eurosurveillance).

So far the H7N9 virus does not appear to be spreading from human to human. This observation suggests that the virus is widespread in poultry in China, and that there have been multiple introductions into humans. It seems likely that these novel viruses arose relatively recently in China and some time thereafter had to opportunity to infect humans.

The question on everyone’s mind is whether the avian influenza H7N9 viruses will acquire the ability to transmit among humans. On this subject the authors have the following comment:

Although human infections with H7 influenza viruses have occurred repeatedly over the last decades without evidence of sustained human-to-human transmission, the absence of sustained human-to-human transmission of A(H7N9) viruses does not come with any guarantee.

It is possible that during replication in birds or humans, the H7N9 viruses might randomly acquire a mutation that allows for transmission. In the right place at the right time, such a virus could spread through the human population. Alternatively, such a transmission-facilitating mutation might interfere with the overall fitness of the virus, thereby preventing it from spreading. I favor the latter hypothesis because the H7N9 viruses have been transmitting since at least February 2013; they have undergone many replication cycles without such a mutation arising. If the virus has not entered wild birds, culling poultry could eradicate it from China – assuming that it has not gone elsewhere.

  • gsgs

    as it reached Germany, it died in 2003. Was it the summer-weather that killed it ?
    I think H7N9 won’t go to wild birds because if is very poultry-like, ~20 amino-acid
    changes in segments 7,8. (as H5N1 HK 1997) You usually won’t see such viruses in
    mallards or shorebirds.
    NL2003 OTOH was similar to mallard viruses.
    The biggest danger IMO is that H7N9 reassorts with H1N1pdm

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  • sammual

    i just confused that why did the virus can transmit from bird to human, however it cannot transmit from human to human? does anything from bird could promote the infection?

  • http://www.virology.ws profvrr

    Good question, for which no one has an answer. Obviously something is different about this virus. Two key differences are in HA and PB2 which allow adaptation to human hosts (see this and the previous blog post).

  • http://www.virology.ws profvrr

    In which animal might H7N9 reassort with H1N1pdm, humans? Swine? (is H7N9 in swine)?

  • gsgs

    it might reassort in humans, China has just a seasonal H1N1-wave.
    H7N9 is probably not in swine yet. It might also reassort in labs deliberately now and escape

  • gsgs

    it may transmit by contact, but not respiratory droplets.Chicken–>finger–>nose or eyes

  • Kathryn Marks

    We talk about reassortment. Is that only in the H and the N areas of the genome? Is the other RNA usually untouched or minimally reassorted. I hope my question is clear, I lack the language to get at what I mean.

  • gsgs

    “small” reassortments (similar segments) happen frequently in poultry H9N2
    and also H7N9 with H9N2 (at least 4 so far). Pandemic danger comes mainly from reassortments.
    that separate HA from most other segments.
    Best candidates to me seem 11171111,17171111 where 1 is mexflu,H1N1pdm
    and 7 is current H7N9

  • sammual

    and in April 3th this year, an H1N1 caused death case was reprort in Yueyang city of Hubei province. http://news.changsha.cn/h/409/20130404/1235400.html

  • formerexpat

    My suspicion is that the current reassortment for H7N9 with mammalian characteristics has made the virus less efficient in its transmission through chickens (how else to explain its low incidence rate of 40 in 40K tested) but not yet made it virulent in mammals, either. This no mans land (pun intended) is putting extreme pressure on the virus, which is why it is seen to be mutating rapidly. We can hope that it mutates back towards its avian hosts. If, on the other hand, the true host turns out to be some other animal (starling, mouse, civet, whatever) then we have to re-think everything.

  • Magpie

    Seems to be at least a few food-prep related cases, so infection via bodily fluids seems a possibility. Might go some way to explaining the weird age distribution, too – apparently retired folk in China do a lot of the food-prep, and the complete lack of identified teenagers might show that Chinese teens are the same as all teens everywhere. :P
    Q226L in HA is a potential worry, and yet… nothing so far. Which is great.

  • gsgs

    it’s not mutating rapidly. Nor did flu ever mutate “backwards” towards birds

  • mediabeam

    Is it just me or is anyone else feeling unhappy/annoyed at the sloppy terminology being used when there are so many fascinating new developments in our nascent science?
    I suspect it is the result of the news media breathing down our necks but already errors and lack of clarity are starting to creep in.

    I think it all dates back to Hong Kong ‘SARS’ in 2003 which was an irritating hijacking of the name of a syndrome to denote a virus! Fair enough most of us thought – we all know what we are talking about.

    Last Sept when Promed posted Prof Ali Mohamed Zaki’s revelation about a novel coronavirus it was promptly sequenced at the EMC and given a scientific name – nCoV(2012)EMC but the media chose to refer to it as the ‘SARS-like virus’ or Novel Coronavirus. The latter was OK except insofaras it will not be ‘novel’ for long! Curiously the popular term ‘Saudi SARS’ is eschewed by the media presumably for political reasons. OK we are pretty clear about that and IF this virus with its ‘unique’ ability to grow in more than one species does mutate and cause a problem that vague epithet can be addressed…

    So now an influenza virus has emerged in China since the New Year and it was soon identified as a mild old avian virus that had never transferred to humans – H7N9. But when the tests came back negative something was different.

    Imagine my reaction when the WHO – quite busy these days one would imagine – published a whole statement saying that:”After broad consultations with experts from FAO, OIE and WHO, a consensus has been reached on the naming of the influenza A(H7N9) virus recently detected in China” Henceforward they are going to call it, er, H7N9.

    Already there is clarification being sought on which test for which virus as old H7N9 is still in birds! Indeed the wise owls (though clearly not virologists) at WHO propose to qualify it with the species name where it was discovered eg avian H7N9 the problem there is that these are in fact different virus and possibly a bird could harbor more than one type.

    Colleagues you will probably chide me for getting hot under the collar about terminology and some might argue that when a virus causes a pandemic we will sort it! You may well be right but ignorance and confusion will I fear hamper efforts to get people organised to cope with the hardships and thwart the virus’s modus operandi and contain it to some degree.

  • FluScientist

    This is how Influenza classification works though. A/Shanghai/1/2013 (this is the actual name for one of the isolates) etc all belong to the H7N9 lineage, despite the few amino acid differences when compared to other H7N9 viruses known to date. The viruses in China have their own specific names, H7N9 only refers to the genotype.

  • FluScientist

    This is how Influenza classification works though. A/Shanghai/1/2013 (this is the actual name for one of the isolates) etc all belong to the H7N9 lineage, despite the few amino acid differences when compared to other H7N9 viruses known to date. The viruses in China have their own specific names, H7N9 only refers to the genotype.

  • FluScientist

    Other gene segments have also been seen in reassorted viruses, like these H7N9 viruses for example (i.e. PB1). Another one came up in Indiana last year and was a triple reassortant containing HA , NA and M genes originally from different viruses.

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