Giuseppe
Emeritus
[Source: World Health Organization, full PDF document: (LINK). Edited.]
Public health relevant virological features of Influenza A(H7N9) causing human infection in China
? World Health Organization 2013
All rights reserved. The Regional Office for Europe of the World Health Organization welcomes requests for permission to reproduce or translate its publications, in part or in full.
The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.
The mention of specific companies or of certain manufacturers? products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.
All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication.
However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. The views expressed by authors, editors, or expert groups do not necessarily represent the decisions or the stated policy of the World Health Organization.
Acknowledgements
WHO/Europe gratefully acknowledges the contributions of WHO collaborating centres, in particular the WHO Collaborating Centre for Reference and Research on Influenza (at the Chinese Center for Disease Control and Prevention) in Beijing, China and the WHO Collaborating Centre for Reference and Research on Influenza (at the National Institute of Infectious Diseases) in Tokyo, Japan for the timely sharing and analysis of data, respectively; and the WHO Collaborating Centre for Reference and Research on Influenza (at the National Institute for Medical Research) in London, United Kingdom, for assistance in the preparation of this document.
Public health relevant virological features of Influenza A(H7N9) causing human infection in China
As of 4 April 2013, the China Health and Family Planning Commission has notified WHO of a total number of eleven (11) confirmed cases of human infection with influenza A(H7N9) virus in China. Five of the 11 cases have died (http://www.who.int/csr/don/2013_04_04/en/index.html ).
This particular strain of A(H7N9) virus has not previously been detected in human or animal populations. WHO is responding to this event, including dissemination of information about the virus in order to support diagnosis, treatment and vaccine development. This document describes some key virological features of the three A(H7N9) viruses analysed so far. These virological features are based on initial analyses carried out by the WHO Collaborating Centres for Reference and Research on Influenza in Beijing and Tokyo, and the WHO Collaborating Centre for Surveillance, Epidemiology and Control of Influenza, Atlanta.
Gene sequences of four viruses have been deposited for A/Shanghai/1/2013, A/Shanghai/2/2013, A/Anhui/1/2013 and A/Hangzhou/1/2013 in GISAID by the WHO Collaborating Centre for Reference and Research on Influenza in Beijing.
Table. Accession numbers in GISAID of A(H7N9) virus gene sequences.
[Gene - A/Shanghai/1/2013 - A/Shanghai/2/2013 - A/Anhui/1/2013 - A/Hangzhou/1/2013]
Possible origin of the virus
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Public health relevant virological features of Influenza A(H7N9) causing human infection in China
? World Health Organization 2013
All rights reserved. The Regional Office for Europe of the World Health Organization welcomes requests for permission to reproduce or translate its publications, in part or in full.
The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.
The mention of specific companies or of certain manufacturers? products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.
All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication.
However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. The views expressed by authors, editors, or expert groups do not necessarily represent the decisions or the stated policy of the World Health Organization.
Acknowledgements
WHO/Europe gratefully acknowledges the contributions of WHO collaborating centres, in particular the WHO Collaborating Centre for Reference and Research on Influenza (at the Chinese Center for Disease Control and Prevention) in Beijing, China and the WHO Collaborating Centre for Reference and Research on Influenza (at the National Institute of Infectious Diseases) in Tokyo, Japan for the timely sharing and analysis of data, respectively; and the WHO Collaborating Centre for Reference and Research on Influenza (at the National Institute for Medical Research) in London, United Kingdom, for assistance in the preparation of this document.
Public health relevant virological features of Influenza A(H7N9) causing human infection in China
As of 4 April 2013, the China Health and Family Planning Commission has notified WHO of a total number of eleven (11) confirmed cases of human infection with influenza A(H7N9) virus in China. Five of the 11 cases have died (http://www.who.int/csr/don/2013_04_04/en/index.html ).
This particular strain of A(H7N9) virus has not previously been detected in human or animal populations. WHO is responding to this event, including dissemination of information about the virus in order to support diagnosis, treatment and vaccine development. This document describes some key virological features of the three A(H7N9) viruses analysed so far. These virological features are based on initial analyses carried out by the WHO Collaborating Centres for Reference and Research on Influenza in Beijing and Tokyo, and the WHO Collaborating Centre for Surveillance, Epidemiology and Control of Influenza, Atlanta.
Gene sequences of four viruses have been deposited for A/Shanghai/1/2013, A/Shanghai/2/2013, A/Anhui/1/2013 and A/Hangzhou/1/2013 in GISAID by the WHO Collaborating Centre for Reference and Research on Influenza in Beijing.
Table. Accession numbers in GISAID of A(H7N9) virus gene sequences.
[Gene - A/Shanghai/1/2013 - A/Shanghai/2/2013 - A/Anhui/1/2013 - A/Hangzhou/1/2013]
- PB2 - EPI439488 - EPI439495 - EPI439504 ? ...
- PB1 - EPI439489 - EPI439501 - EPI439508 ? ...
- PA - EPI439490 - EPI439498 - EPI439503 ? ...
- HA - EPI439486 - EPI439502 - EPI439507 ? EPI440095
- NP - EPI439491 - EPI439496 - EPI439505 ? ...
- NA - EPI439487 - EPI439500 - EPI439509 ? EPI44096
- M - EPI439493 - EPI439497 - EPI439506 ? EPI440097
- NS - EPI439494 - EPI439499 - EPI439510 ? ...
Possible origin of the virus
- It is considered likely that the new virus stems from a reassortment of three virus strains that infect only birds:
- The 6 genes coding for the internal proteins are similar to recent H9N2 viruses found in China and South Korea. H9N2 viruses are endemic in birds, including poultry, in Asia and elsewhere.
- The gene for the N protein is similar to avian H11N9 viruses found in South Korea in 2011; in Hongze, Jiangsu, in 2010; and in the Czech Republic in 2005.
- The gene for the H protein belongs to a Eurasian group of H7 avian influenza viruses.
- However, the reservoir for these viruses infecting humans may or may not be poultry.
- The HA gene sequences do not encode the hall-mark of a highly pathogenic avian influenza (HPAI) virus, this being a series of basic amino acids at the HA1/HA2 cleavage site; rather they encode a single arginine at this site as found in low pathogenic avian influenza (LPAI) virus.
- This finding suggests that infections in poultry could be mild or silent and thus go unnoticed. Pathogenicity of the virus needs to be confirmed by the intravenous pathogenicity index test in 6-week old chicks (http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.03.04_AI.pdf ).
- Three findings suggest that these influenza A( H7N9) viruses have undergone adaptation to mammalian hosts:
- The HA gene sequences of two of the isolates encode leucine at residue 217 of HA1 and another carries isoleucine at this position, the equivalent of residue 226 in HA1 of H3-HA containing viruses, indicative of recognition of sialic acid linked α2-6 to galactose which is present in the upper respiratory tract of humans and other mammals.
- The stalk region of the NA has a deletion of 5 amino acids. Substitutions in the NA stalk are frequently observed on the transfer of viruses from wild fowl to poultry or mammals.
- The PB2 gene of each virus encodes an E627K substitution. This change is associated with improved replication of avian influenza viruses in mammals.
- The NA gene of one of the four genetically characterized viruses encodes a R292K substitution which has been associated with oseltamivir and zanamivir resistance in NAs of other subtypes. However, this is not a universal marker for resistance to neuraminidase inhibitors in influenza A viruses (see PMID 21253602, table 1).
- Phenotypic assessment of the sensitivity of these three influenza A(H7N9) viruses has shown them to be sensitive to oseltamivir and zanamivir.
- The M genes of the viruses encode S31N substitution. An asparagine at residue 31 is consistent with resistance to amantadine and rimantadine. This finding has yet to be confirmed by phenotypic assay.
- Antigenic properties of these A(H7N9) viruses relative to existing potential vaccine candidates, largely dependent on their H7-HA components, have yet to be determined.
- Current H7 candidate vaccine viruses are not expected to be cross-protective and candidate vaccine viruses based on the A(H7N9) virus will be developed.
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