Composition of the Hemagglutinin Polybasic Proteolytic Cleavage Motif Mediates Variable Virulence of H7N7 Avian Influenza Viruses

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Abstract

Acquisition of a polybasic cleavage site (pCS) in the hemagglutinin (HA) is a prerequisite for the shift of low pathogenic (LP) avian influenza virus (AIV) to the highly pathogenic (HP) form in chickens. Whereas presence of a pCS is required for high pathogenicity, less is known about the effect of composition of pCS on virulence of AIV particularly H7N7. Here, we investigated the virulence of four avian H7N7 viruses after insertion of different naturally occurring pCS from two HPAIV H7N7 (designated pCSGE and pCSUK) or from H7N1 (pCSIT). In vitro, the different pCS motifs modulated viral replication and the HA cleavability independent on the HA background. However, in vivo, the level of virulence conferred by the different pCS varied significantly. Within the respective viral backgrounds viruses with pCSIT and pCSGE were more virulent than those coding for pCSUK. The latter showed also the most restricted spread in inoculated birds. Besides the pCS, other gene segments modulated virulence of these H7N7 viruses. Together, the specific composition of the pCS significantly influences virulence of H7N7 viruses. Eurasian LPAIV H7N7 may shift to high pathogenicity after acquisition of “specific” pCS motifs and/or other gene segments from HPAIV.

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A review of avian influenza in different bird species.

Dennis Alexander (2000)

Only type A influenza viruses are known to cause natural infections in birds, but viruses of all 15 haemagglutinin and all nine neuraminidase influenza A subtypes in the majority of possible combinations have been isolated from avian species. Influenza A viruses infecting poultry can be divided into two distinct groups on the basis of their ability to cause disease. The very virulent viruses cause highly pathogenic avian influenza (HPAI), in which mortality may be as high as 100%. These viruses have been restricted to subtypes H5 and H7, although not all viruses of these subtypes cause HPAI. All other viruses cause a much milder, primarily respiratory disease, which may be exacerbated by other infections or environmental conditions. Since 1959, primary outbreaks of HPAI in poultry have been reported 17 times (eight since 1990), five in turkeys and 12 in chickens. HPAI viruses are rarely isolated from wild birds, but extremely high isolation rates of viruses of low virulence for poultry have been recorded in surveillance studies, giving overall figures of about 15% for ducks and geese and around 2% for all other species. Influenza viruses have been shown to affect all types of domestic or captive birds in all areas of the world, but the frequency with which primary infections occur in any type of bird depends on the degree of contact there is with feral birds. Secondary spread is usually associated with human involvement, probably by transferring infective faeces from infected to susceptible birds.

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Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands.

Marion Koopmans, Berry Wilbrink, Marina Conyn … (2004)

An outbreak of highly pathogenic avian influenza A virus subtype H7N7 started at the end of February, 2003, in commercial poultry farms in the Netherlands. Although the risk of transmission of these viruses to humans was initially thought to be low, an outbreak investigation was launched to assess the extent of transmission of influenza A virus subtype H7N7 from chickens to humans. All workers in poultry farms, poultry farmers, and their families were asked to report signs of conjunctivitis or influenza-like illness. People with complaints were tested for influenza virus type A subtype H7 (A/H7) infection and completed a health questionnaire about type of symptoms, duration of illness, and possible exposures to infected poultry. 453 people had health complaints--349 reported conjunctivitis, 90 had influenza-like illness, and 67 had other complaints. We detected A/H7 in conjunctival samples from 78 (26.4%) people with conjunctivitis only, in five (9.4%) with influenza-like illness and conjunctivitis, in two (5.4%) with influenza-like illness only, and in four (6%) who reported other symptoms. Most positive samples had been collected within 5 days of symptom onset. A/H7 infection was confirmed in three contacts (of 83 tested), one of whom developed influenza-like illness. Six people had influenza A/H3N2 infection. After 19 people had been diagnosed with the infection, all workers received mandatory influenza virus vaccination and prophylactic treatment with oseltamivir. More than half (56%) of A/H7 infections reported here arose before the vaccination and treatment programme. We noted an unexpectedly high number of transmissions of avian influenza A virus subtype H7N7 to people directly involved in handling infected poultry, and we noted evidence for person-to-person transmission. Our data emphasise the importance of adequate surveillance, outbreak preparedness, and pandemic planning.

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TOPALi v2: a rich graphical interface for evolutionary analyses of multiple alignments on HPC clusters and multi-core desktops

Iain Milne, Dominik Lindner, Micha Bayer … (2008)

Summary: TOPALi v2 simplifies and automates the use of several methods for the evolutionary analysis of multiple sequence alignments. Jobs are submitted from a Java graphical user interface as TOPALi web services to either run remotely on high-performance computing clusters or locally (with multiple cores supported). Methods available include model selection and phylogenetic tree estimation using the Bayesian inference and maximum likelihood (ML) approaches, in addition to recombination detection methods. The optimal substitution model can be selected for protein or nucleic acid (standard, or protein-coding using a codon position model) data using accurate statistical criteria derived from ML co-estimation of the tree and the substitution model. Phylogenetic software available includes PhyML, RAxML and MrBayes. Availability: Freely downloadable from http://www.topali.org for Windows, Mac OS X, Linux and Solaris. Contact: iain.milne@scri.ac.uk

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Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group

ISSN (Electronic): 2045-2322

Publication date (Electronic): 22 December 2016

Publication date Collection: 2016

Volume: 6

Electronic Location Identifier: 39505

Affiliations

[1 ]Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health , Greifswald-Insel Riems, Germany

[2 ]Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health , Greifswald-Insel Riems, Germany

[3 ]Institute of Epidemiology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health , Greifswald-Insel Riems, Germany

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[a ] sayed.abdel-whab@ 123456fli.bund.de

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Publisher Item ID: srep39505

DOI: 10.1038/srep39505

PMC ID: 5177941

PubMed ID: 28004772

SO-VID: b63e0f3e-f59e-4f5f-b888-be4872675825

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This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Composition of the Hemagglutinin Polybasic Proteolytic Cleavage Motif Mediates Variable Virulence of H7N7 Avian Influenza Viruses

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Abstract

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Genes & Diseases

Most cited references 28

A review of avian influenza in different bird species.

Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands.

TOPALi v2: a rich graphical interface for evolutionary analyses of multiple alignments on HPC clusters and multi-core desktops

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