Why is there poor correlation between Indonesian Bird and Human HA sequences?

[JJackson]

We have all been pushing for sequence release and, very slowly, this has been occurring. The net result seems to be we now have an incomplete phylogenic tree with enough data in it to indicate that there is poor correlation between the Indonesian H5N1 human & poultry sequences. In fact - as I understand it ? the sequence data from pigs, wildfowl, cats etc. when added to the tree seems to be making it more, rather than less, difficult to ?see? a path to human infection.

WHO has always tried to implicate poultry as a possible source of infection - sometimes tortuously - in a rather bizarre attempt to preclude h2h speculation.

I am aware ? from the discussions on MDCK/egg culturing ? that with cycling the binding/cleavage site specificity may be selectively changed but as I understand it this would not account for other changes in the HA sequence and so would not be adequate to account for the separations within the tree.

Is the correlation better if the trees are produced for other RNA fragments? (so far as these have been sequenced and released).


Is anyone ready to propose a hypothesis that can account for this discrepancy?

 

[HenryN]

Re: Why is there poor correlation between Indonesian Bird and Human HA sequences?

The Ministry of Health in Indonesia has confirmed the country's 52nd case of human infection with the H5N1 avian influenza virus.

The case, which was fatal, occurred in a 5-year-old boy from Tulungagung district, East Java Province. The boy became ill on 8 June, was hospitalized on 14 June and died two days later on 16 June.

An investigation found a history of chicken deaths in the boy's household two weeks before symptom onset. Laboratory testing of poultry in the sub-district confirmed the presence of H5N1 in chickens. Monitoring of close contacts has detected no further cases.

Of the 52 cases confirmed to date in Indonesia, 40 have been fatal.

http://www.who.int/csr/don/2006_07_04/en/index.html

 

[wetDirt]

Re: Why is there poor correlation between Indonesian Bird and Human HA sequences?

I know we don't have much information on what different animals have been screened in Indonesia, but I'm aware of cat/tiger, dog, swine, and various birds including pigeons, seabirds, and goose/duck/chicken type birds. I would be really interested to know whether rats, mice, and bats have been tested, and what the results were. It seems like RNA viruses like bats in particular; they are a known reservoir for rabies, along with suspected for ebola and SARS. It would make sense for the unknown vector for Influenza to be nocturnal, because humans aren't, and tend to focus on species they see in the daytime. We've always been weak on what goes on at night. If the unknown reservoir isn't human, then we have a problem.

Another explanation for the difference in the polybasic cleavage site is that there is a problem with sample collection, storage, handling, and analysis between human samples and veterinary samples. It would also be nice to know more about the sampling protocols, and whether we are somehow shooting ourselves in the foot. I've had experience before with different labs running the same test with different substrates, and not being able to compare the results.

I'm betting on there being an overlooked reservoir, but I'm not ready to rule out lab artifacts, either. It sure would be nice if they released a few more sequences.

 

[HenryN]

Re: Why is there poor correlation between Indonesian Bird and Human HA sequences?

Another explanation for the difference in the polybasic cleavage site is that there is a problem with sample collection, storage, handling, and analysis between human samples and veterinary samples. It would also be nice to know more about the sampling protocols, and whether we are somehow shooting ourselves in the foot. I've had experience before with different labs running the same test with different substrates, and not being able to compare the results.

I'm betting on there being an overlooked reservoir, but I'm not ready to rule out lab artifacts, either. It sure would be nice if they released a few more sequences.

I think artifacts can be safely ruled out. The differences in the HA cleavage site conveniently labels the differences, but they go well beyond the cleavage site and these additional differences are reflected in the different arms of the phylogenetic trees.

There may be differences in what samples are collected, and poor handling/testing could generate false negatives, but not closely related sequences. The human sequences are generated independently by Hong Kong and the CDC. Hong Kong also does much of the bird sequencing and recent sequences from Nidom or various groups (in Germany and Indonesia) show the same results.

The human H5N1 is quite distinct from the various avian H5N1's although all are easily assigned to Indonesia.

 

[JJackson]

Re: Why is there poor correlation between Indonesian Bird and Human HA sequences?

There is a cat sample which is close enough to the human samples to be a plausible host resevoir but the cats I have heard of that were tested, were tested because they died. Is anyone aware of asymptomatic positives from cats? If not cats then humans, what is the current consensus view on asymptomatic humans? There was a report which seemed to indicate a surprising lack of antibodies in the contacts of H5N1 victims followed by Dr Nidom?s view that seemed to imply he thought there were many.

 

[Mingus]

Re: Why is there poor correlation between Indonesian Bird and Human HA sequences?

Frankly, my first tought was that swine was the source of this cleavage site.

For the cleavage site to be different and not seen elsewhere in other host, a mid-long isolated evolution(without trans-speacies) should have taken place.

But If there is no sustained h-2-h transmission, it must be a reservoir somewhere.

Ok sampling and ckecking in indonesia is poor amongs the poor but...

It seem that recent swine sequence do not show this RESKKR so I'm confused.

Where is that reservoir ?

 

[AlaskaDenise]

Re: Why is there poor correlation between Indonesian Bird and Human HA sequences?

Might we be seeing mutations from HIV infected humans? Prostitutes?

Remember that HIV-infected humans won't have overactive immune systems and could survive. They are known to take far longer to clear ordinary flu - providing a medium for further mutations.

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