Cited by 663Influenza Virus Research StudiesVirology and Viral DiseasesViral Infections and Outbreaks Research

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Role of hemagglutinin cleavage for the pathogenicity of influenza virus.

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Steinhauer, David A.·1999·Virology

DOI 10.1006/viro.1999.9716

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Abstract

Although human epidemics of influenza occur on nearly an annual basis and result in a significant number of "excess deaths," the viruses responsible are not generally considered highly pathogenic. On occasion, however, an outbreak occurs that demonstrates the potential lethality of influenza viruses. The human pandemic of 1918 spread worldwide and killed millions, and the limited human outbreak of highly pathogenic avian viruses in Hong Kong at the end of 1997 is a warning that this could happen again. In avian species such as chickens and turkeys, several outbreaks of highly pathogenic influenza viruses have been documented. Although the reason for the lethality of the human 1918 viruses remains unclear, the pathogenicity of the avian viruses, including those that caused the human 1997 outbreak, relates primarily to properties of the hemagglutinin glycoprotein (HA). Cleavage of the HA precursor molecule HA0 is required to activate virus infectivity, and the distribution of activating proteases in the host is one of the determinants of tropism and, as such, pathogenicity. The HAs of mammalian and nonpathogenic avian viruses are cleaved extracellularly, which limits their spread in hosts to tissues where the appropriate proteases are encountered. On the other hand, the HAs of pathogenic viruses are cleaved intracellularly by ubiquitously occurring proteases and therefore have the capacity to infect various cell types and cause systemic infections. The x-ray crystal structure of HA0 has been solved recently and shows that the cleavage site forms a loop that extends from the surface of the molecule, and it is the composition and structure of the cleavage loop region that dictate the range of proteases that can potentially activate infectivity. Here influenza virus pathogenicity is discussed, with an emphasis on the role of HA0 cleavage as a determining factor.

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Zambon, M. C. (2001) · Reviews in Medical Virology · doi:10.1002/rmv.319 · Cited by 186

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Authors: Steinhauer, D. A.
Affiliations: National Institute for Medical Research (GB)
Corresponding author: Steinhauer, David A.
ORCID: Steinhauer, David A.
Venue: Virology
Publisher: Elsevier BV
Published: 1999-05
Volume: 258
Issue: 1
Pages: 1-20
ISSN: 0042-6822 (ISSN-L)
DOI: 10.1006/viro.1999.9716
OpenAlex: W2006079378
Cited by: 663
References: 236
Citations by year: 2026: 14 · 2025: 13 · 2024: 16 · 2023: 19 · 2022: 17 · 2021: 36 · 2020: 50 · 2019: 30 · 2018: 20 · 2017: 24 · 2016: 32 · 2015: 25 · 2014: 36 · 2013: 43 · 2012: 37
FWCI: 8.04
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 5191 d)
Locations: Virology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
Keywords: influenza virus, hemagglutinin cleavage, pathogenicity, proteolytic cleavage sites, host tropism, 1918 influenza pandemic, highly pathogenic avian influenza, viral infectivity
MeSH terms: Animals, Binding Sites, Enzyme Activation, Glycoproteins, Humans, Orthomyxoviridae, Endopeptidases, Protein Precursors, Viral Proteins, Hemagglutinin Glycoproteins, Influenza Virus

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Role of hemagglutinin cleavage for the pathogenicity of influenza virus.

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