The DOI matches its Crossref record; 236 of the 236 references it cites were found in a registry or an index.
Role of hemagglutinin cleavage for the pathogenicity of influenza virus.
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Evolution and ecology of influenza A viruses
Webster, R. G., Bean, W. J., Gorman, O. T., Chambers, T. M., & Kawaoka, Y. (1992) · Microbiological Reviews · doi:10.1128/mr.56.1.152-179.1992 · Cited by 4,739
Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolution
Wilson, I. A., Skehel, J. J., & Wiley, D. C. (1981) · Nature · doi:10.1038/289366a0 · Cited by 2,537
Structure of influenza haemagglutinin at the pH of membrane fusion
Bullough, P. A., Hughson, F. M., Skehel, J. J., & Wiley, D. C. (1994) · Nature · doi:10.1038/371037a0 · Cited by 1,564
Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus
Claas, E. C. J., Osterhaus, A. D. M. E., van Beek, R., de Jong, J. C., Rimmelzwaan, G. F., Senne, D. A., Krauss, S. L., Shortridge, K. F., & Webster, R. G. (1998) · The Lancet · doi:10.1016/s0140-6736(97)11212-0 · Cited by 1,420
THE STRUCTURE AND FUNCTION OF THE HEMAGGLUTININ MEMBRANE GLYCOPROTEIN OF INFLUENZA VIRUS
Wiley, D. C., & Skehel, J. J. (1987) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.56.070187.002053 · Cited by 1,413
Subbarao, K., Klimov, A. I., Katz, J. M., Regnery, H. L., Lim, W., Hall, H. E., Perdue, M. L., Swayne, D. E., Bender, C. A., Huang, J., et al. (1998) · Science · doi:10.1126/science.279.5349.393 · Cited by 1,353
Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid
Weis, W. I., Brown, J. H., Cusack, S., Paulson, J. C., Skehel, J. J., & Wiley, D. C. (1988) · Nature · doi:10.1038/333426a0 · Cited by 1,162
Cold Spring Harbor Symposia on Quantitative Biology.
Berg, H. (1989) · Journal of Electroanalytical Chemistry · doi:10.1016/0022-0728(89)87283-3 · Cited by 1,152
Yuen, K., Chan, P., Peiris, M. J. S., Tsang, D., Que, T., Shortridge, K. F., Cheung, P., To, W., Ho, E., Sung, R. Y. T., et al. (1998) · The Lancet · doi:10.1016/s0140-6736(98)01182-9 · Cited by 1,054
Molecular Basis for the Generation in Pigs of Influenza A Viruses with Pandemic Potential
Ito, T., Couceiro, J. N. D. S. S., Kelm, S., Baum, L. G., Krauss, S. L., Castrucci, M. R., Donatelli, I., Kida, H., Paulson, J. C., Webster, R. G., et al. (1998) · Journal of Virology · doi:10.1128/jvi.72.9.7367-7373.1998 · Cited by 1,029
Flagged first, then by citations
Research works printed but not linked: 7
- Alexandrova, 1965, Obtaining an additionally attenuated vaccinating cryophilic influenza strain, Rev. Roum. Inframicrobiol., 2, 179
- Carlisle, 1947, The effect of influenza virus on the susceptibility of white mice toStreptococcus hemolyticus, J. Bact., 53, 503
- Cross, G. M. 1986, The status of avian influenza in poultry in Australia, In, Proceedings of the Second Annual Symposium on Avian Influenza, 96, 103
- Eckroade, R. I. Bachin, L. A. 1987, Avian influenza in Pennsylvania: The beginning, In, Proceedings of the Second International Symposium on Avian Influenza, Easterday, B. C. 22, 32, US Animal Health Association, Richmond
- Schwab, 1941, The response of mice to nasal inoculation of mixtures ofStreptococcus hemolyticus, J. Bact., 41, 59
- Steinhauer, 1992, Receptor binding and cell entry by influenza viruses, Semin. Virol., 3, 91
- US Animal Health Association, 1994, Report of the Committee on Transmissible Diseases of Poultry and Other Avian Species: Criteria for determining that an AI virus isolation causing an outbreak must be considered for eradication, In, Proceedings of the 98th Annual Meeting, 522, US Animal Health Association, Grand Rapids, MI
Cited by
Sorted by citations
Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein
Walls, A. C., Park, Y.-J., Tortorici, M. A., Wall, A., McGuire, A. T., & Veesler, D. (2020) · doi:10.1101/2020.02.19.956581 · Cited by 8,586
Secondary bacterial infections associated with influenza pandemics
Morris, D. E., Cleary, D. W., & Clarke, S. C. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.01041 · Cited by 576
Wrobel, A. G., Benton, D. J., Xu, P., Roustan, C., Martin, S. R., Rosenthal, P. B., Skehel, J. J., & Gamblin, S. J. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0468-7 · Cited by 544
Realities and enigmas of human viral influenza: pathogenesis, epidemiology and control.
HILLEMAN, M. (2002) · Vaccine · doi:10.1016/s0264-410x(02)00254-2 · Cited by 319
The pathogenesis of influenza in humans.
Zambon, M. C. (2001) · Reviews in Medical Virology · doi:10.1002/rmv.319 · Cited by 186
Metadata
- 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)
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
