China - H7N9 Human Isolates on Deposit at GISAID

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

AND.... Harbin (Huihui Kong) shared a.... pigeon on GISAID!
Perhaps next they'll share one of those quails.

Now we can all await more analysis by the global scientific community.

The NS1/103 & 106 has the same values as the chicken and humans.

The pigeon HA is most similar to people and chicken in China, but then a Korean wild bird, Mongolian duck, and poultry from Europe???

Hopefully this newest data will help more scientists put their collective minds to work on this newcomer virus.

.

The Shanghai Wet Market Surveillance H7N9 sequences are detailed for comprehensive HA and NA amino acid variation including references to direct H5N1 multi-species mammal homology at post #30.

[camster]

Re: China - H7N9 Human Isolates on Deposit at GISAID

Camster thank you so much for taking the time to add some depth to my rather superficial understanding of the realities of testing. In light of your post then what I really want to see is if their has been an uptick in the samples with a low CT score that do not subtype, which would weed out any weak samples that were just strong enough to score a hit on the type A test but too weak to give a positive against a serotype specific primer.

Regarding the second paragraph I find it helpful when trying to understand what is going on in a host to think of it infecting individual cells. Transmission to a new host is very much the exception to the rule. For every released virion 99.99% are going to infect another cell in the same host the one(s) that seed a new host are very much a Columbus or Vasco da Gama. As many generations of infection, replication and reinfection are taking place in the same host there is also plenty of scope for the generation of new reassortments, recombinations and SNPs. Unless a particular change keeps cropping up in different hosts I normally work on the assumption it has been generated locally and is just a normal by-product of the quasi-species aspect of flu. As flu, like all viruses, is an obligate parasite the cost of producing all those dodgy copies is born by the host so it is no great loss to the virus if its RNP is somewhat lacking in quality control.

good thoughts!

Those type of results SHOULD be reported up the chain and I would hope most labs are acting responsibly, especially in light of what is going on in China.

Transmission is key to the virus, if it only stays in one host, it will eventually die off with it. It must jump to new hosts and if it needs a dodgy polymerase to help out with that, then evolution will keep the polymerase dodgy. This is one time the old microsoft joke (It's not a bug, it's a feature!) is true

but yes, transmission within the host is much more efficient, given it's sort of a captive audience until the immune system really kicks in. We saw how fast pH1N1 spread around the world. I think the rate limiting step is pre-existing immunity, not getting sneezed out of the nose onto someone else.

[camster]

Re: China - H7N9 Human Isolates on Deposit at GISAID

Thanks for the explanations. Tis good to read the implications of a promiscuous pathogen.

Might the "fixed mutations" vary within an individual host, depending on the immune genetics of any one part of the body?, e.g., the P53 gene can be active in one area and silenced in another, thereby influencing the virus' ability to replicate differently in different locations, as the NS1 segment interacts with downstream parts of P53 which control growth arrest and apoptosis.

.

Certainly possible, we certainly see variations from individuals in the same platoon or the same family unit. I think some if it might be luck of the draw, but whenever I start to think that, I remind myself that nature is not lazy and rarely wastes effort.

But different receptors in different tissues etc. could certainly contribute to a situation like that. I'm not sure if anyone has ever compared the sequence found orally with those in the lower tract or shed via the fecal route. Hrm..I'll have to look.

[camster]

Re: China - H7N9 Human Isolates on Deposit at GISAID

Are any of the cases gravid?

I noticed one case mentioned today on Promed (apologies if someone already answered this), 25Y female.

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

I noticed one case mentioned today on Promed (apologies if someone already answered this), 25Y female.

Much appreciated, Camster.

Confirmed H7N9

1. 85M, Critical Care
2. 25F Pregnant, Critical Care
3. 64M, Fatal in 6 days

• Human infection with influenza A(H7N9) virus in China - update -WHO Announcement
• Subject: PRO/AH/EDR> Avian influenza, human (38): China (SH, JS) H7N9 update - ProMed

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

Certainly possible, we certainly see variations from individuals in the same platoon or the same family unit. I think some if it might be luck of the draw, but whenever I start to think that, I remind myself that nature is not lazy and rarely wastes effort.

But different receptors in different tissues etc. could certainly contribute to a situation like that. I'm not sure if anyone has ever compared the sequence found orally with those in the lower tract or shed via the fecal route. Hrm..I'll have to look.

Nature is specific. Tropism, even collection method, invokes predictable variation across pH1N1.

What do you think about the avian H7 culling of 3 million birds around Jalisco that started in March?

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

good thoughts!

Those type of results SHOULD be reported up the chain and I would hope most labs are acting responsibly, especially in light of what is going on in China.

Transmission is key to the virus, if it only stays in one host, it will eventually die off with it. It must jump to new hosts and if it needs a dodgy polymerase to help out with that, then evolution will keep the polymerase dodgy. This is one time the old microsoft joke (It's not a bug, it's a feature!) is true

but yes, transmission within the host is much more efficient, given it's sort of a captive audience until the immune system really kicks in. We saw how fast pH1N1 spread around the world. I think the rate limiting step is pre-existing immunity, not getting sneezed out of the nose onto someone else.

Carrying your rate limiting step further, would you find the fact of the average Chinese citizen having a higher everyday multiplicity of exposure to circulating avian strains (live domestic poultry) to be an advantage over the average American's zero-level, pre-existing immunity to this novel, emergent H7N9?

We find very few HA epitopes that are suggestive of cross-reactivity between traditional first world exposures, Σ[sH3N2, pH1N1, B], and this H7N9 emergence.

[AlaskaDenise]

Re: China - H7N9 Human Isolates on Deposit at GISAID

.....But different receptors in different tissues etc. could certainly contribute to a situation like that. I'm not sure if anyone has ever compared the sequence found orally with those in the lower tract or shed via the fecal route. Hrm..I'll have to look.

The specific situation that might apply is that of a human with worsening esophageal disease. Early on, the inflammation caused by GERD or Barrett's esophagus can silence the P53 gene, which would facilitate AI infections. Of course, that same mutation during metastatsis, dysplasia, and eventually carcinoma would have the same effect. Given that this progression can take roughly 25 years, that could be a lot of years that some people's esophagus is more able to facilitate AI infectivity. China has one of the highest rates (10-100 times the US) of esophageal cancer, so that might have some bearing on this issue.

This issue of maintaining a robust immune system really means we should all do what is necessary to keep those genes functioning. Those silenced genes CAN be reactivated through diet.

.

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

The specific situation that might apply is that of a human with worsening esophageal disease. Early on, the inflammation caused by GERD or Barrett's esophagus can silence the P53 gene, which would facilitate AI infections. Of course, that same mutation during metastatsis, dysplasia, and eventually carcinoma would have the same effect. Given that this progression can take roughly 25 years, that could be a lot of years that some people's esophagus is more able to facilitate AI infectivity. China has one of the highest rates (10-100 times the US) of esophageal cancer, so that might have some bearing on this issue.

This issue of maintaining a robust immune system really means we should all do what is necessary to keep those genes functioning. Those silenced genes CAN be reactivated through diet.

.

Well said.

The paramount imperative that all families should take during this potential worldwide emergence is balancing immune function by re-activating silenced genetics and routing past primary genetic failures to backup immune genes.

[AlaskaDenise]

Re: China - H7N9 Human Isolates on Deposit at GISAID

Studies have shown the foods needed to correct silenced (abberant methylation) genes in the immune system & elsewhere are here.

.

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

Matter of Notifiable Interest
from the GeneStack

The following statement is NOT a GeneWurx prediction, but is a matter of concern that we consider notifiable to public health authorities.

The concept is strictly preliminary as we have seen no clinicals, lab work, treatment modalities, or well-structured epidemiology, much less autopsy material. Clinical progression, specific organ systems attacked with order of attack and lytic intensity would be useful factors in weighing the next statement. Let's arrange the labs to spend more time gathering and evaluating actual data and less time taking averages and making spurious projections when sample populations obviously remain invalid, e.g. the recent quote that H7N9 has a "mutation rate 8 times higher".

Though the potential is not quantifiable at this time, we ask the world community to look slightly beyond the current H7N9 and examine one probable facet of viral reservoir adjustment to low transmissibility. We clearly have a competent HA becoming mammal-adapted that is seated against an agonist NA segment that is less adapted. And the question certainly remains of how much less mammal-adapted the NA is?

If this competent HA becomes less interested in the dead-ending, a potential exists for a reassortment to a more capable and compatible NA. The founding genetics of this current emanation of emergent H7N9 demonstrates multiple signal pathways toward N2 affinity with nominal secondary potential for mammal N8. The Gain of Function scalability ranges from the potentially lower risk H9N2 to the significantly higher risk donation from the circulating Vaccine-Escape, High-CFR H3N2.

That circulating human H3N2 has overseen mortality rates in the United States between 5 and 17 times last season's totals and between 200% and 300% of the previous state records in the states of Indiana, Minnesota and Pennsylvania. Though H3N2 is a long "understood" serotype with a multi-decade history of vaccine production, in the state of Indiana this year, 39% of the fatalities had confirmed vaccinations and another 34% conveniently were annotated as an "unknown" status. Only 27% of the fatalities were confirmed unvaccinated. Our reports from 2013 Week 13 (cumulative) are attached to this post.

The emergent H7N9 cases, while not 80% over 60 years old, demonstrate a weighting toward older citizens. Does this emergent H7N9 have something in common with the circulating human H3N2 that describes this affinity for older hosts or is the age skewing a small population anomaly that will self-correct as the sample size increases? If the emergent H7N9 does, in fact, prove to have interchange behaviour with sH3N2, will a convergent H3N2 NA reassortment be an attractive option to this competent HA and the currently stable 6 internal genes of the emergent H7N9?

More importantly, should we re-access the serotype testing that was done in states with double to triple the previous state record fatality counts? Human H3N2 has shown extensive signals of co-infection during the entire Northern Hemisphere season. Does the possibility exist that re-testing those samples may demonstrate a background level of H7 in a fraction of the cases.

Time to open the freezers.

And while the doors are opened, would someone please organise the sequencing and publication of the following sample types for any date between 2008 and today:

• China, Avian / Quail, 48 Samples geographically diverse, incl. a series within a single host individual.
• Thailand, Avian / Quail, 20 Samples
• Vietnam, Avian / Quail, 18 Samples
• Hong Kong, Avian / Quail, 16 Samples
• Cambodia, Avian / Quail, 10 Samples
• Singapore, Avian / Quail, 8 Samples

These samples will fill the gaps in the data record and, in high probability, pinpoint the effectors to this emergence.

[AlaskaDenise]

Re: China - H7N9 Human Isolates on Deposit at GISAID

I hope H3N2 isn't programmed to read this forum.

.

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

Consolidation from another thread, Is H7N9 Spreading from Human to Human in China?

There may a yet-undiscovered connection with the 8 Asian Human H5N1 2011 cases - all containing 627K. Bangladesh=1, Cambodia=2, Singapore=5.

.

Cross Serotype Homology
Hemagglutinin Amino Polymorphisms
Emergent H7N9 to H5N1 Human 2011

We acknowledge the authors, originating and submitting laboratories of the sequences from GISAID’s EpiFlu™ Database on which this research is based. The list is detailed in the attached PDF entitled "GISAID_Citations_H5N1_2011" at Is H7N9 Spreading from Human to Human in China? Post#164

You are right on target. From a population of 38 human HA sequences in the H5N1 serotype in 2011, we find the following homology between human H5N1 2011 and human H7N9. The details were reported in a wider format at the noted post on this thread.

1. HA 189A WildType all 2011
2. HA 202V China Fatal 2008 (1), 2011 (1), 2012 (1), 2013 (2), Recovered 2009 (2) / Egypt Human 2011 / Vietnam Fatal 2004 (1), Human (4)
3. HA 277N WildType all 2011
4. HA 401N WildType all 2011, except Indonesia (3)
5. HA 533V WildType all 2011, except Indonesia (4)

Verify HA 189A, 202V, 277N, 401N, 533V (~H7 198A, 211V, 285N, 410N, 541V) at GeneWurx Cross Serotype Homology - Post #12

H5N1 2011 also shows polymorphic behaviour at related positions of HA 313T (Cambodia), 401S (Indonesia) & 533I (Indonesia).

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

Studies have shown the foods needed to correct silenced (abberant methylation) genes in the immune system & elsewhere are here.

.

In addition to the broccoli, all cruciferous vegetables deliver indoles, including cauliflowers and cabbages, . Remember to eat your stalks. Leafy greens like kale, turnip, mustard and collard greens deliver similar indole-3-carbinol and are most richly bioassimilable when sauteed in a fully saturated lipid prior to simmering in a stock.

We evaluate plants as well as viral species. Some nerds eschew the pizza pocket for the Portugeuse Kale Soup.

[JJackson]

Re: China - H7N9 Human Isolates on Deposit at GISAID

I have a process question and this thread seem as good a place as any to ask it.

Assume an infection has taken place in a host that is applying some level of selection pressure on the flu virus and a range of mutations has been generated. As the infection progresses those best adapted to the new host predominate and at some point a good sneeze produces a droplet containing many virions which form a representative subset of the host's strains. The droplet in question then seeds an infection in the new host.

The question is: Is it generally thought that only one of these virions seed the infection from which the new host generates its own quasi-species or that having got down into the URT more than one of the virions in the droplet generally manage to enter one (or more) of the epithelial cells? In other words do you start with a mixture or just generate one form a unique sequence set?

It is something I had always wondered about but never seen discussed.