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

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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  • Several strains of S. aureus produce proteases that cleave influenza HA, increasing vRNP entry into host cells and overall progeny virions.

    “Several strains of S. aureus produce proteases that cleaves influenza HA; the more protease that is available, the more HA can be cleaved meaning more vRNP can get into host cells meaning overall more progeny virions (Tashiro et al., 1987; Steinhauer, 1999; Samji, 2009).”

    From Secondary bacterial infections associated with influenza pandemics (2017) · cites this paper as Steinhauer, 1999

  • The low pH in the endosome causes a conformational change to HA allowing it to be cleaved, an important step in penetrating into the host cell; HA and availability of appropriate host proteases are determinants of infectivity.

    “The low pH in the endosome causes a conformational change to the HA allowing it to be cleaved, an important step in penetrating into the host cell. Therefore HA and the availability of appropriate host proteases are determinants of infectivity (Steinhauer, 1999; Samji, 2009).”

    From Secondary bacterial infections associated with influenza pandemics (2017) · cites this paper as Steinhauer, 1999

  • Non-pathogenic and mammalian influenza HA undergoes cleavage outside of the host cell, whereas highly pathogenic strains are cleaved inside host cells.

    “Interestingly non-pathogenic and mammalian influenza HA undergoes cleavage outside of the host cell where as highly pathogenic strains are cleaved inside host cells (Steinhauer, 1999).”

    From Secondary bacterial infections associated with influenza pandemics (2017) · cites this paper as Steinhauer, 1999

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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
Licence
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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