H7N9 flu peril lies in deep lung infiltration: study

[tetano]

PARIS ? The H7N9 bird flu virus is a peril for humans because it replicates deep in the lungs where it can trigger a dangerous response from the immune system, a study said Wednesday.

In addition, no one is likely to have pre-existing immunity to H7N9 and so-called seasonal vaccines cannot protect against it, the study said, confirming suspicions among many virologists.

And while lab tests show that leading anti-flu drugs are effective, there are concerns the virus may acquire gene mutations to blunt these weapons, it added.

The study, published in Nature by the Chinese Centre for Disease Control and Prevention (CDC) in Beijing, delved into the genetic ID of the virus which emerged in China in February.

The virus has been characterised by severe symptoms of pneumonia and respiratory distress, with a high fatality rate, especially among the elderly.

There have been 131 confirmed cases of H7N9 in China, with at least 40 fatalities, according to Chinese figures. An additional case of illness occurred in Taiwan, involving a man who had been working in China.

H7N9 has a shape of receptor, or docking point, that enables it to latch onto cells in the lining of the lower respiratory tract and replicate there, the investigators said.

...

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[tetano]

Re: H7N9 flu peril lies in deep lung infiltration: study

The original article

 

[tetano]

Re: H7N9 flu peril lies in deep lung infiltration: study

H7N9 Bird Flu Transmits From Person to Person, Study Finds
But it's not easily spread and public should not panic, expert says


WEDNESDAY, July 3 (HealthDay News) -- Contrary to previously published reports, the deadly H7N9 bird flu can spread from person to person and may be a serious threat to humans, Chinese health officials report.

The virus, which has killed one-third of the patients hospitalized with it, attaches itself to cells in the windpipe and lungs, infecting even cells lodged deep in the respiratory system, said researchers who analyzed the biological features of the virus.

This dual-target binding may make the virus better able to jump from birds to humans, according to their report, which was published July 3 in the journal Nature.

"The new virus has a unique binding property," said lead researcher Yuelong Shu, director of the Chinese National Influenza Center at the China CDC in Beijing.

...


http://health.usnews.com/health-new...u-transmits-from-person-to-person-study-finds

 

[sharon sanders]

Re: H7N9 flu peril lies in deep lung infiltration: study

hat tip Michael Coston

Nature: Biological Features Of H7N9



Credit CDC


# 7444


A study, published today in the Journal Nature, provides new insights into the H7N9 avian flu virus which emerged on the Chinese mainland earlier this spring, and suggests that should it return this winter, it could prove a far more formidable foe than than has H5N1 to date.

Chinese researchers, looking both at the virus in the laboratory, and at patient responses to infection, have concluded that this virus `poses a potentially high risk to humans.?.
​

Among their findings:

• Unlike the H5N1 virus ? which binds preferentially to avian receptor cells (a2,3-linked sialic acid) - H7N9 binds to both the avian and human (a2,6-linked sialic acid) receptor cells.

• This dual receptor cell binding ability likely enhances the virus?s ability to transmit from birds to humans.

• The virus appears to replicate well in the lower human respiratory tract - but less well in the trachea ? which may have helped to limit its ability to spread from human-to-human.

• Once infected, the virus often produces severe illness in humans, and patients tested showed increased serum levels of chemokines and cytokines, suggesting the possibility of infection inducing a `cytokine storm?.

• There appears to be little or no community immunity to H7 viruses.

First, a link to the letter in Nature (the abstract is available, but the whole letter is behind a pay wall). Given the barebones nature of the abstract, I?ll return with a little more backgroundon some of their findings.

Biological features of novel avian influenza A (H7N9) virus



Jiangfang Zhou1*,DayanWang1*,RongbaoGao1*, Baihui Zhao2*, Jingdong Song1,XianQi3 ,Yanjun Zhang4, Yonglin Shi 5, LeiYang1, Wenfei Zhu1, Tian Bai 1,KunQin1, Yu Lan1, Shumei Zou1, JunfengGuo1, JieDong1 , LiboDong1 ,Ye Zhang1, HejiangWei 1, Xiaodan Li 1, Jian Lu1 , Liqi Liu1 , Xiang Zhao1, Xiyan Li 1, Weijuan Huang1, LeyingWen1 ,HongBo1 , Li Xin1, Yongkun Chen1 , Cuilin Xu1, Yuquan Pei 6,YueYang6 , Xiaodong Zhang6, ShiwenWang1, Zijian Feng7 , JunHan7 ,Weizhong Yang7, George F. Gao7 , GuizhenWu1 ,Dexin Li 1, Yu Wang7 & Yuelong Shu1 ​

Highlighting a few points raised by this study.

The authors note that H7N9:`. . .can invade epithelial cells in the human lower respiratory tract and type II pneumonocytes in alveoli . . ?.

Pneumocytes (aka pneumonocytes) are a collective term for the two types of cells lining the alveoli (the air sacs) in the lung; Type I and Type II pneumocytes.

• Type I pneumocytes are responsible for the gas exchange (02 and C02) between the lungs and the blood stream. Type I pneumocytes are easily damaged and cannot reproduce themselves.

• Type II pneumocytes are responsible for the production of surfactant, which reduces the surface tension of pulmonary fluids and contributes to the elasticity of the lungs.

• Type II pneumocytes are able to replicate in the alveoli and can create new Type I pneumocytes.

A loss of type II pneumocytes can severely degrade the lungs ability to fight off an infection, and to repair damaged tissue. Earlier studies have demonstrated tropism for, and destruction of, type II pneumocytes by the avian H5N1 virus.

While still only partially understood, the idea behind a `cytokine storm? is that the host?s immune system goes into overdrive, producing excessive levels of cytokines that can provoke damaging inflammation in the lungs.

Cytokines are a category of signaling molecules that are used extensively in cellular communication. They are often released by immune cells that have encountered a pathogen, and are designed to alert and activate other immune cells to join in the fight against the invading pathogen.
​

This cascade of immune cells rushing to the infection, if it races out of control, can literally kill the patient. Their lungs can fill with fluid (which makes a terrific medium for a bacterial co-infection), and cells in the lungs (Type 1 & Type II Pneumocytes) can sustain severe damage.

Previously, in Swine Flu Sequelae and Cytokine Storm Warnings,we looked at some of the severe lung damage during the 2009 pandemic that was thought to be due to this overreaction of the immune system.

You can find more on this theory in these earlier posts:

Study: Calming The Cytokine Storm

Cytokine Storm Warnings

The Baskin Influenza Pathogenesis Study
Pt. 1 Pt. 2 Pt. 3
​

Another finding (across all age groups tested) was a lack of pre-existing immunity to the H7N9 virus, and that the current seasonal vaccine conveyed absolutely no protection.

As we?ve discussed earlier, while work is underway on creating seed strains for an H7N9 vaccine, getting one through the testing and manufacturing process and into the arms of hundreds of millions of people, is unlikely to happen in the near term (see JAMA: Challenges Of Producing An Effective & Timely H7N9 Vaccine).
​

For now, the saving grace with this virus is its apparent inability to spread efficiently from human-to-human. But should that change, the world could find itself facing a particularly nasty pandemic threat.

Posted by Michael Coston at <a class="timestamp-link" href="http://afludiary.blogspot.ca/2013/07/nature-biological-features-of-h7n9.html" rel="bookmark" title="permanent link"><abbr class="published" title="2013-07-03T14:39:00-04:00">2:39 PM</abbr>

 

[Giuseppe]

Re: H7N9 flu peril lies in deep lung infiltration: study

On this same issue and related to pathogenicity in mammals:

Source: US National Library of Medicine, full page: http://www.ncbi.nlm.nih.gov/pubmed/2...?dopt=Abstract - Abstract on FluTrackers.com: http://www.flutrackers.com/forum/sho...868#post502868

• Low pathogenic avian influenza A(H7N9) virus causes high mortality in ferrets upon intratracheal challenge: A model to study intervention strategies.
  • Kreijtz JH, Kroeze EV, Stittelaar KJ, de Waal L, van Amerongen G, van Trierum S, van Run P, Bestebroer T, T Kuiken, Fouchier RA, Rimmelzwaan GF, Osterhaus AD.
  • Vaccine. 2013 Jun 28. pii: S0264-410X(13)00880-3.
  • doi: 10.1016/j.vaccine.2013.06.071. [Epub ahead of print]
  • PMID: 23816392 [PubMed - as supplied by publisher]

Source: mBio, full page: http://mbio.asm.org/content/4/4/e00362-13.short?rss=1 - Abstract on FluTrackers.com: http://www.flutrackers.com/forum/sho...813#post502813

• Pathogenicity of the Novel A/H7N9 Influenza Virus in Mice.
  • Chris Ka Pun Mok, Horace Hok Yeung Lee, Michael Chi Wai Chan, Sin Fun Sia, Maxime Lestra, John Malcolm Nicholls, Huachen Zhu, Yi Guan, Joseph Malik Sriyal Peiris.
  • mBio 4(4):e00362-13.
  • doi:10.1128/mBio.00362-13.

Source: US National Library of Medicine, full text: http://www.ncbi.nlm.nih.gov/pubmed/2...?dopt=Abstract - Abstract on FluTrackers.com: http://www.flutrackers.com/forum/sho...990#post501990

• Receptor binding by an H7N9 influenza virus from humans.
  • Xiong X, Martin SR, Haire LF, Wharton SA, Daniels RS, Bennett MS, McCauley JW, Collins PJ, Walker PA, Skehel JJ, Gamblin SJ.
  • Nature. 2013 Jun 20.
  • doi: 10.1038/nature12372. [Epub ahead of print]
  • PMID: 23787694 [PubMed - as supplied by publisher]

Source: Cell, full text: http://www.cell.com/abstract/S0092-8674(13)00640-5 - Abstract on FluTrackers.com: http://www.flutrackers.com/forum/sho...515#post500515

• Glycan Receptor Binding of the Influenza A Virus H7N9 Hemagglutinin.
  • Kannan Tharakaraman, Akila Jayaraman, Rahul Raman, Karthik Viswanathan, Nathan W. Stebbins, David Johnson, Zachary Shriver, V. Sasisekharan, Ram Sasisekharan.
  • Cell, 06 June 2013.
  • Doi: 10.1016/j.cell.2013.05.034

Source: Science, full text: http://www.sciencemag.org/content/ea...f-5a84c8836de2 - On FluTrackers.com: http://www.flutrackers.com/forum/sho...772#post498772

• Infectivity, Transmission, and Pathology of Human H7N9 Influenza in Ferrets and Pigs.
  • H. Zhu, D. Wang, D. J. Kelvin, L. Li, Z. Zheng, S.-W. Yoon, S.-S. Wong, A. Farooqui, J. Wang, D. Banner, R. Chen, R. Zheng, J. Zhou, Y. Zhang, W. Hong, W. Dong, Q. Cai, M. H. A. Roehrl, S. S. H. Huang, A. A. Kelvin, T. Yao, B. Zhou, X. Chen, G. M. Leung, L. L. M. Poon, R. G. Webster, R. J. Webby, J. S. M. Peiris, Y. Guan, Y. Shu.
  • DOI: 10.1126/science.1239844

Source: US National Library of Medicine, full page: http://www.ncbi.nlm.nih.gov/pubmed/23628410?dopt=Abstract - On FluTrackers.com: http://www.flutrackers.com/forum/showthread.php?p=495724#post495724

• Genomic signature and protein sequence analysis of a novel influenza A (H7N9) virus that causes an outbreak in humans in China.
  • Liu Q, Lu L, Sun Z, Chen GW, Wen Y, Jiang S.
  • Microbes Infect. 2013 Apr 26. pii: S1286-4579(13)00085-3. doi: 10.1016/j.micinf.2013.04.004. [Epub ahead of print]

________

Full list http://www.flutrackers.com/forum/showthread.php?t=203472

 

[Shiloh]

H7N9 flu peril lies in deep lung infiltration

H7N9 flu peril lies in deep lung infiltration

Source: http://www.globalpost.com/dispatch/news/afp/130703/h7n9-flu-peril-lies-deep-lung-infiltration


Agence France-Presse
July 3, 2013 15:33
H7N9 flu peril lies in deep lung infiltration

The H7N9 bird flu virus is a peril for humans because it replicates deep in the lungs where it can trigger a dangerous response from the immune system, a study said Wednesday.

In addition, no one is likely to have pre-existing immunity to H7N9 and so-called seasonal vaccines cannot protect against it, the study said, confirming suspicions among many virologists...

 

[Shiloh]

Re: H7N9 flu peril lies in deep lung infiltration

Re: H7N9 flu peril lies in deep lung infiltration

Source: http://health.yahoo.net/news/s/hsn/h7n9-bird-flu-transmits-from-person-to-person-study-finds

H7N9 Bird Flu Transmits From Person to Person, Study Finds
By Steven Reinberg
HealthDay Reporter, HealthDay
Jul. 03, 2013 2:00PM PDT

WEDNESDAY, July 3 (HealthDay News) -- Contrary to previously published reports, the deadly H7N9 bird flu can spread from person to person and may be a serious threat to humans, Chinese health officials report.

The virus, which has killed one-third of the patients hospitalized with it, attaches itself to cells in the windpipe and lungs, infecting even cells lodged deep in the respiratory system, said researchers who analyzed the biological features of the virus.

This dual-target binding may make the virus better able to jump from birds to humans, according to their report, which was published July 3 in the journal Nature...

 

[Giuseppe]

Re: H7N9 flu peril lies in deep lung infiltration: study

The above mentioned article title is a bit misleading since the study points fingers toward the dual receptors binding affinity of the novel avian influenza virus H7N9 - able to latch avian-like and human-like spikes in respiratory epithelium cells - and thus demonstrating the better adaptation of the virus to mammals.

Human-to-human transmission is a strong possibility and possibly happened during the recent epidemic in China.

The issue is the 'community transmission': until the virus is not fully adapted to humans, a sustained interhuman spread remains difficult.

Epidemiological surveillance is the key: to spot as early as possible the signs of a such community spread in order to share with international community the start of the sustained human-to-human transmission and the subsequent rise in pandemic alert level response.

Other papers(1) recently published showed that the H7N9 virus binds strongly to the avian-like receptors, retaining this feature may represent a restraint for an impending adaptation toward a pandemic strain. This window of opportunity may be closing so that international agencies should use this time to prepare for a future pandemic better than in the past. (GM)

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(1) Nature. 2013 Jun 20. doi: 10.1038/nature12372. Receptor binding by an H7N9 influenza virus from humans. Xiong X, Martin SR, Haire LF, Wharton SA, Daniels RS, Bennett MS, McCauley JW, Collins PJ, Walker PA, Skehel JJ, Gamblin SJ.


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