Perspectives on Research with H5N1 Avian Influenza Scientific Inquiry, Communication, Controversy: Summary of a Workshop (2013) / Chapter Skim
Currently Skimming:
Appendix C: The Two Published H5N1 Papers
Appendix C: The Two Published H5N1 Papers
Pages 81-100
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 81... ...
"Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets," Sander Herfst, et al., Science 336 (June 22, 2012)
|
From page 82... ...
However, because humans laboratory-adapted human influenza A virus. lack immunity to influenza viruses possessing an H5 HA, the emergence Turkey red blood cells (TRBCs; which possess both Siaa2,6Gal and of a transmissible H5-HA-possessing virus would probably cause a Siaa2,3Gal on their surface (data not shown)
|
From page 83... ...
Thus, only one H5 HA variant with receptor-binding VN1203/PR8 virus (possessing an avirulent HA cleavage site sequence, capability akin to that of seasonal influenza viruses was isolated from as described earlier)
|
From page 84... ...
K173/PR8, VN1203/PR8 and mutant VN1203/PR8 viruses were incubated To assess the effect of enhanced a2,6-glycan recognition on the mutants exhibited strong binding to the ciliated epithelial cells of the attachment of viruses to human respiratory tracts, sections of tracheal trachea (Fig. 2c and Supplementary Fig.
|
From page 85... ...
Three ferrets per group were killed on days 3 human-to-human transmission is a critical feature of pandemic and 6 after infection for virus titration. Virus titres in nasal turbinates, trachea influenza viruses, we examined the growth and transmissibility of and lung were determined by use of a plaque assay on MDCK cells.
|
From page 86... ...
Collectively, these findments32, rgCA04 was efficiently transmitted via respiratory droplets ings demonstrate that four amino acid substitutions (N158D/N224K/ to all three contact ferrets, as evidenced by the detection of virus in Q226L/T318I) in H5 HA confer efficient respiratory droplet transmisnasal washes and haemagglutination inhibition (HI)
|
From page 87... ...
level of stability of the HA protein in an acidic environment, as the pH Nasal washes were collected every other day from both inoculated (left panel) of human nasal mucosa, where human influenza viruses replicate and contact (right panel)
|
From page 88... ...
/CA04 human reassortant viruses. a, Representative histological changes in nasal turbinates from influenza-virus-infected ferrets.
|
From page 89... ...
One of the four muta- use by the CDC and the USDA. Ferret transmission studies were conducted by three scientists with both DVM and PhD degrees who each had more than a tions we identified in our transmissible virus, the N158D mutation, minimum of 6 years of experience with highly pathogenic influenza viruses and results in loss of a glycosylation site.
|
From page 90... ...
et al. Identification of amino acids in HA and PB2 critical for the by the University of Wisconsin-Madison Responsible Official and at regular inter- transmission of H5N1 avian influenza viruses in a mammalian host.
|
From page 91... ...
assay for currently targeted mutation rate (1–2 amino acid replacements per molecule) was achieved circulating human influenza viruses.
|
From page 92... ...
. The statistical significance of differences between rgCA04 and H5 determined by use of plaque assays in MDCK cells and haemagglutination assays avian/human reassortant viruses was determined by using a Dunnett's test.
|
From page 93... ...
that binds to viral RNA and, Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far together with the polymerase proteins, forms the has not acquired the ability to be transmitted by aerosol or respiratory droplet ("airborne transmission") ribonucleoprotein complexes (RNPs)
|
From page 94... ...
nose swabs collected can be further classified into highly pathogenic daily until day 4, from avian influenza (HPAI) and low-pathogenic avian ferrets inoculated with influenza (LPAI)
|
From page 95... ...
, and there are cause they are susceptible to infection with human from only four pandemics are available for analy- concerns that this virus could acquire molecular and avian influenza viruses (24)
|
From page 96... ...
6. Comparison of airborne transmission of experimental passaged A/H5N1 and 2009 pandemic demic influenza viruses (29–31)
|
From page 97... ...
. personnel were instructed and trained extensive- type influenza viruses, as this switch contributed Because the mutant virus harboring the ly for working in the ABSL3+ facility, handling to the emergence of the 1957 and 1968 pan- E627K mutation in PB2 and Q222L and G224S (highly pathogenic)
|
From page 98... ...
For this purpose, nasal-wash quence of parental virus isolated from F2. inoculated with A/H5N1HA Q222L,G224S PB2 E627K samples were diluted 1:2 in PBS and subsequent- Together, these results suggest that as few as virus, a moderate increase in virus titers in the ly used to inoculate six naïve ferrets intranasally: five amino acid substitutions (four in HA and one nasal turbinates was observed as the passage two for passage 10 A/H5N1wildtype and four for in PB2)
|
From page 99... ...
Moreover, previous infections of hu- Substitutions Q222L and G224S have pre- tion T156A in HA has been reported in >50% of mans with seasonal influenza viruses are likely to viously been shown to be sufficient to switch the viruses sequenced and was detected in 100% induce heterosubtypic immunity that would offer receptor-binding specificity of avian influenza of the viruses from human cases in Egypt (53)
|
From page 100... ...
. Avian A/H5N1 influenza viruses pose a pandemic threat.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.