China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

[Catbird]

"H7N9 bird flu may mutate 8 times faster than regular flu, study finds

10 April, 2013

The new bird flu could be mutating up to eight times faster than an average flu virus around a protein that binds it to humans, a team of research scientists in Shenzhen says.

Dr He Jiankui, an associate professor at South University of Science and Technology of China, said yesterday that the authorities should be alarmed by the results of their research and step up monitoring and control efforts to prevent a possible pandemic.

With genetic code of the virus obtained from mainland authorities, the team scrutinised haemagglutinin, a protein that plays a crucial rule in the process of infection. The protein binds the virus to an animal cell, such as respiratory cells in humans, and bores a hole in the cell's membrane to allow entry by the virus.

The researchers found dramatic mutation of haemagglutinin in one of the four flu strains released for study by the central government. Nine of the protein's 560 amino acids had changed. In a typical flu virus, only one or two amino acids could change in such a short period of time, He said.

"It happened in just one or two weeks. The speed may not have caught up with the HIV, but it's quite unusual for a flu."

The fast mutation makes the virus' evolutionary development very hard to predict. "We don't know whether it will evolve into something harmless or dangerous," He said. "Our samples are too limited. But the authorities should definitely be alarmed and get prepared for the worst-case scenario."

The origin of the virus was puzzling due to its novelty, but He's research suggested some clues that differ from the mainland authorities' theories.

His team compared the new virus strain to all other H7N9 viruses identified in Europe and in other Asian countries that were cited by the Ministry of Agriculture as possible origins of the new bird flu, but found them all very different.

In fact, the new bird flu was quite similar to some familiar domestic viruses such as H9N2, H11N9 and H7N3 found in Zhejiang and Jiangsu.

He said researchers could not rule out the possibility that the new virus was carried into China by wild birds, but it was more likely to be of local origin."

http://www.scmp.com/news/china/arti...mutate-8-times-faster-regular-flu-study-finds

 

[jflorida]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

Origins and evolutionary genomics of the novel 2013 avian-origin H7N9 influenza A virus in China: Early findings [ http://arxiv.org/abs/1304.1985 ]

The whole Paper :

Origins and evolutionary genomics of the novel 2013
avian-origin H7N9 influenza A virus in China: Early findings
Jiankui He*, Luwen Ning, Yin Tong
Department of Biology, South University of Science and Technology of China, Shenzhen, China,
518055

[ http://arxiv.org/ftp/arxiv/papers/1304/1304.1985.pdf ]



Although the A-OIV has been reported in just one week, we already observed substantial new
mutations in their genome (Fig. 2). Within the four newly sequenced genomes, the HA protein of
A/Shanghai/1/2013 strains have 9 amino acid mutations compared to 3 other strains
(Supplemental Fig. 18). This indicates that the A-OIV has significant capability to mutate, which
increases our concern that the high mutation rate may lead to the change of transmissibility and
virulence

 

[jflorida]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

This cant be good with respect to vaccine production cat. I wonder what mechanism specifically is causing the high mutation rate.

 

[Vibrant62]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

Agreed. And universal vaccines are still some way off

 

[Vibrant62]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

I also wonder if the high mutation rate would elevate risks of rapid development of anti-viral drug resistance.

 

[jflorida]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

I cant think of a reason why it wouldn't. I wonder if can even reinfect the same person.

 

[Pirante]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

Perhaps this is the reason the cdc is already taking measures to control the outbreak?

 

[AlaskaDenise]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

This cant be good with respect to vaccine production cat. I wonder what mechanism specifically is causing the high mutation rate.

Is it possible that it may appear to be a fast mutation, but is actually a case of missing puzzle pieces? The sequences in databases are such a tiny sample of the actual cases that it's hard to make any reliable hypothesis at this point.

The PB2/E627K mystery was bothering me so much that I started searching through all the mammal sequences in a blast of the Shanghai human case, then after finding no unexpected 627 data, I looked through ALL birds in GenBank since 1-1-2011. There was ONE wild bird sampled in Korea which had a 627K! So if we can find one "illogical" transmission in our little databases, imagine how many more are in the total wild population.

.

 

[AlaskaDenise]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

but it was more likely to be of local origin[/U].[/B]" ...

That may be little less true for the NA - it looks like it's been on an international cruise with many ports. At the higher levels of similarity, it's sharing genes from Czech Republic, Australia, Hokkaido, Spain, siberia, Mongolia, Sweden, Netherland, Switzerland. The Chinese WHO submitted this NA sequence to GISAID, so this supports their statements it came partly from wild birds.

.

 

[solitaire]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

Hi, I'm a bit confused on this. In the report on early findings above, http://arxiv.org/ftp/arxiv/papers/1304/1304.1985.pdf, the NA is from H11N9 A/mallard/Czech Republic/13438-29k/2010 with 95% identity but in an article here http://www.thestandard.com.hk/news_...5&sid=39434004&con_type=1&d_str=20130410&fc=4
it says ........"A research paper of the laboratory reported by mainland media Caixin suggested that out of the eight genes found in the H7N9 virus, the H7 gene was traced from ducks in the eastern province of Zhejiang and the N9 gene was identical to a virus found in wild birds from South Korea".

No doubt someone has already covered this elsewhere on the forum, but which is correct and what is the South Korean virus?

 

[Toaster2]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

deleted, see post below

 

[Toaster2]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

I am not aware of these 9 HA mutations in one of the 4 sequences at GSIAD, but maybe I missed it. Can someone enlighten me ? Thanks !

"H7N9 bird flu may mutate 8 times faster than regular flu, study finds

10 April, 2013

The new bird flu could be mutating up to eight times faster than an average flu virus around a protein that binds it to humans, a team of research scientists in Shenzhen says.

Dr He Jiankui, an associate professor at South University of Science and Technology of China, said yesterday that the authorities should be alarmed by the results of their research and step up monitoring and control efforts to prevent a possible pandemic.

With genetic code of the virus obtained from mainland authorities, the team scrutinised haemagglutinin, a protein that plays a crucial rule in the process of infection. The protein binds the virus to an animal cell, such as respiratory cells in humans, and bores a hole in the cell's membrane to allow entry by the virus.

The researchers found dramatic mutation of haemagglutinin in one of the four flu strains released for study by the central government. Nine of the protein's 560 amino acids had changed. In a typical flu virus, only one or two amino acids could change in such a short period of time, He said.

"It happened in just one or two weeks. The speed may not have caught up with the HIV, but it's quite unusual for a flu."

The fast mutation makes the virus' evolutionary development very hard to predict. "We don't know whether it will evolve into something harmless or dangerous," He said. "Our samples are too limited. But the authorities should definitely be alarmed and get prepared for the worst-case scenario."

The origin of the virus was puzzling due to its novelty, but He's research suggested some clues that differ from the mainland authorities' theories.

His team compared the new virus strain to all other H7N9 viruses identified in Europe and in other Asian countries that were cited by the Ministry of Agriculture as possible origins of the new bird flu, but found them all very different.

In fact, the new bird flu was quite similar to some familiar domestic viruses such as H9N2, H11N9 and H7N3 found in Zhejiang and Jiangsu.

He said researchers could not rule out the possibility that the new virus was carried into China by wild birds, but it was more likely to be of local origin."

http://www.scmp.com/news/china/arti...mutate-8-times-faster-regular-flu-study-finds

 

[jflorida]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"


Classical H7N9 viruses have been reported as early as 1999. We found that A
- OIV and classic H7N9 share less similarity compared
to other strains such as H7N3 and H7N1. Therefore, the A
- OIV is not likely mutated from the classical H7N9. Together, our results show that the A
- OIV is a new virus that stems from a reassortment of three avian
influenza virus strains and the reassortment events likely happened in
the eastern China.

Although the A-OIV has been reported in just one week, we already observed substantial new mutations in their genome (Fig. 2). Within the four newly sequenced genomes, the HA protein of A/Shanghai/1/2013 strains have 9 amino acid mutations compared to 3 other strains (Supplemental Fig. 18). This indicates that the A-OIV has significant capability to mutate, which
increases our concern that the high mutation rate may lead to the change of transmissibility and virulence.


That was a human case I think. So is there a possibility of two or more viruses, previously undetected, infecting humans and occurring in the same region. and/or existing in that region for a period of no known large outbreaks in animals or humans and undetected?

I suppose its possible. The recent animal deaths could have heightened sensitivity too. I think the rapid mutation is a better theory but whatever the case it will be verifiable with more observation.

 

[jflorida]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

Top Chinese lab reveals H7N9 source [ http://news.xinhuanet.com/english/china/2013-04/10/c_132299005.htm ]

According to the researchers, the genetic reassortment is likely to have occurred in east China's Yangtze River Delta areas covering Shanghai, Zhejiang and Jiangsu.

The lab's research shows the H7 and N9 gene segments in H7N9 are similar to those in avian influenza samples collected from wild birds from east Asia, while the other six genes are traceable to chickens in China's Shanghai, Zhejiang and Jiangsu.

As to why the H7N9 is less harmful to the animals than to humans, researchers said it's because of viral mutation, adding that they had monitored the mutation of the N9 genes.

 

[curiosity]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

Please, correct me if I am way off base here - this is my attempt to understand the "mutate 8 times faster" concept.

Is the opportunity for mutation based on the ability to evolve/replicate in a host?

Is the rapidity of evolution dependent upon the virus genetics alone - i.e., Strain A will reproduce at x per hour, but Strain B will reproduce at (10x) per hour?
Or is the actual viral replication a constant?

Is the rapidity of evolution dependent on the available host? I.e., if there are more hosts, there is more replication/evolution?

If the last is true, then would the ability for this virus to mutate 8 times faster indicate there is a large reservoir of hosts?

 

[JimO]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

If this is the case, then it has acquired the ability to infect humans quite rapidly.

Top Chinese lab reveals H7N9 source [ http://news.xinhuanet.com/english/china/2013-04/10/c_132299005.htm ]

According to the researchers, the genetic reassortment is likely to have occurred in east China's Yangtze River Delta areas covering Shanghai, Zhejiang and Jiangsu.

The lab's research shows the H7 and N9 gene segments in H7N9 are similar to those in avian influenza samples collected from wild birds from east Asia, while the other six genes are traceable to chickens in China's Shanghai, Zhejiang and Jiangsu.

As to why the H7N9 is less harmful to the animals than to humans, researchers said it's because of viral mutation, adding that they had monitored the mutation of the N9 genes.

 

[jflorida]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

PB2 changes I guess they saw.

Viruses can change so fast a increased mutation rate isnt necessarily a good thing for them - I dont know if the 8 x is a max "in theory" kinda thing or what.

Mutation rates among RNA viruses - 1999 [ http://www.pnas.org/content/96/24/13910.full ]

 

[NS1]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

post incomplete.

More later.

 

[Shiloh]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

Source: http://www.newscientist.com/article/dn23368-china-bird-flu-may-be-two-mutations-from-a-pandemic.html

China bird flu may be two mutations from a pandemic
17:21 10 April 2013 by Debora MacKenzie
F
In China, nine people have died and more than 20 are seriously ill in the latest outbreak of bird flu, H7N9. And there are fears that the death toll could rise much higher because the virus already has three of the five mutations that we know could allow another bird flu, H5N1, to spread between mammals...

 

[jflorida]

Re: China: Researchers in Hong Kong suggest that "H7N9 bird flu may mutate 8 times faster than regular flu"

Tamiflu-Resistance Gene in H7N9 Bird Flu Spurs Drug Tests [ http://www.bloomberg.com/news/2013-...e-gene-in-h7n9-bird-flu-spurs-drug-tests.html ]

A gene mutation known to help influenza resist Tamiflu was found in the first of three H7N9 bird-flu patient specimens in China, sequence data show.

The flu virus from the patient in Shanghai has a mutation known as R292K that causes high-level resistance to the Roche Holding AG (ROG) pill and reduced sensitivity to a related drug from GlaxoSmithKline Plc (GSK) called Relenza, genetic sequence information posted on the website of the Global Initiative on Sharing Avian Influenza Data show. Subsequent H7N9 specimens from a patient in Shanghai and one in Anhui province don’t show the mutation.

Preliminary tests so far show no evidence that the new flu strain, which has sickened at least 33 people, killing nine, in eastern China, has developed resistance to the neuraminidase inhibitor drugs Tamiflu and Relenza, the World Health Organization said in a statement yesterday.
“When you look at the raw data and compare the three strains of the virus, there’s a signal from one strain that it’s less sensitive to both of the neuraminidase inhibitors,”


Neuraminidase Inhibitors May Work When Tamiflu Doesn't February 21, 2013 [ http://cen.acs.org/articles/91/i8/Neuraminidase-Inhibitors-Work-Tamiflu-Doesnt.html ]

The new agents, devised by a University of British Columbia-based team, inhibit the flu virus enzyme neuraminidase. They halt the spread of flu viruses in cell culture and animal tests, including strains resistant to the commercial flu drug Tamiflu, which also inhibits neuraminidase. The compounds could therefore lead to a Tamiflu backup drug.

neuraminidase catalyzes sialic acid cleavage by a mechanism involving a covalent intermediate. They determined the structure of the intermediate and designed sialic acid analogs that bond covalently to the viral neuraminidase active site but release very slowly, thus disabling it, and do not inhibit human neuraminidase. The compounds may evade viral resistance more effectively than Tamiflu because their structures more closely resemble that of sialic acid. Also, covalent bonding permanently inactivates the neuraminidase active site; Tamiflu and the three other inhibitors bind noncovalently.


Mechanism-Based Covalent Neuraminidase Inhibitors with Broad-Spectrum Influenza Antiviral Activity [ http://www.sciencemag.org/content/340/6128/71 ]


First H7N9 patient discharged from hospital, more recovering [ http://news.xinhuanet.com/english/china/2013-04/10/c_132298381.htm ]

Lu Hongzhou, a professor with the Shanghai Public Health Clinic Center, said clinical observations have found that if a H7N9 patient can be given treatment no later than five days after he or she shows flu symptoms, China's current therapeutic methods can be effective in treating the disease.

"Over five days, the patient's visceral organs can be damaged, and the medicines like oseltamivir will have little effect on the patient," Lu said.

Doctors with the Pediatric Hospital affiliated to Fudan University, one of Shanghai's designated hospitals for taking H7N9 patients, said they did not use a large dose of antiviral drugs on the boy in order to minimize the side effects.



Note: Oseltamivir is marketed under the trade name Tamiflu.