Insertion of a multibasic cleavage site in the haemagglutinin of human influenza H3N2 virus does not increase pathogenicity in ferrets.

Eefje J A Schrauwen¹ Theo M Bestebroer¹ Vincent J Munster^2,1 Emmie de Wit^2,1 Sander Herfst¹ Guus F Rimmelzwaan¹ Albert D M E Osterhaus¹ Ron A M Fouchier¹

Affiliations 2 institutions

National Influenza Center and Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.

PMID21346026 DOI10.1099/vir.0.030379-0 Year2011 Journal The Journal of general virology J Gen Virol Languageeng Publication statusActive

Active Last checked 2026-10-08 03:30:36 Source: NCBI PubMed

Abstract

A multibasic cleavage site (MBCS) in the haemagglutinin (HA) protein of influenza A virus is a key determinant of pathogenicity in chickens, and distinguishes highly pathogenic avian influenza (HPAI) viruses from low pathogenic avian influenza viruses (LPAI). An MBCS has only been detected in viruses of the H5 and H7 subtypes. Here we investigated the phenotype of a human H3N2 virus with an MBCS in HA. Insertion of an MBCS in the H3N2 virus resulted in cleavage of HA and efficient replication in Madin-Darby canine kidney cells in the absence of exogenous trypsin in vitro, similar to HPAI H5N1 virus. However, studies in ferrets demonstrated that insertion of the MBCS into HA did not result in increased virus shedding, cellular host range, systemic replication or pathogenicity, as compared with wild-type virus. This study indicates that acquisition of an MBCS alone is insufficient to increase pathogenicity of a prototypical seasonal human H3N2 virus.

Supporting text Virus Host Location

Ferrets 79 Mutagenesis, Insertional 3 Animals 1981 Cell Line 162 Dogs 181 Hemagglutinin Glycoproteins, Influenza Virus 183 Humans 1455 Influenza A Virus, H3N2 Subtype 49 Orthomyxoviridae Infections 235 Protein Processing, Post-Translational 4 Virus Replication 195

Evidence records

1 total

Experimental Infection

1 records · 1 evidence types

Evidence type Pathogenicity Experiment

1 records

OVE942 Pathogenicity Experiment

Key finding

Insertion of a multibasic cleavage site in the HA of human H3N2 influenza virus did not increase pathogenicity, virus shedding, or systemic replication in ferrets compared with the wild-type virus.

Virus

Host

Location

Supporting text

Studies in ferrets demonstrated that insertion of the MBCS into HA did not result in increased virus shedding, cellular host range, systemic replication or pathogenicity, as compared with wild-type virus.

Method: experimental infection of ferrets | assessment of virus shedding | evaluation of systemic replication and pathogenicity
Experimental system: ferret infection model

References

41 references

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Evidence overview

Evidence 1

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Types 1

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Linked entities

Viruses

Hosts

domestic ferret Mustela putorius furo

Locations

Publication metadata

Journal: The Journal of general virology
Volume / Issue / Pages: 92 / Pt 6 / 1410-1415
ISSN: 1465-2099
Journal country: England
DOI: 10.1099/vir.0.030379-0