Evidence map›Paper›PMID 34959552›Full record

ArticlePathogens (Basel, Switzerland)2021

Structural Requirements in the Hemagglutinin Cleavage Site-Coding RNA Region for the Generation of Highly Pathogenic Avian Influenza Virus.

Yurie Kida, Kosuke Okuya, Takeshi Saito, Junya Yamagishi, Aiko Ohnuma, Takanari Hattori, Hiroko Miyamoto, Rashid Manzoor, Reiko Yoshida, Naganori Nao and 3 more

Open access · goldAbstract read
In one paragraph

Article in Pathogens (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.4field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 17 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Yurie KidaDivision of Global Epidemiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
Kosuke OkuyaDivision of Global Epidemiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.ORCID 0000-0002-7987-9884
Takeshi SaitoDivision of Global Epidemiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.ORCID 0000-0002-6908-0702
Junya YamagishiDivision of Collaboration and Education, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
Aiko OhnumaTechnical Office, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
Takanari HattoriDivision of Global Epidemiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
Hiroko MiyamotoDivision of Global Epidemiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
Rashid ManzoorDivision of Global Epidemiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.ORCID 0000-0001-8834-2707
Reiko YoshidaDivision of Global Epidemiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
Naganori NaoDivision of International Research Promotion, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
Masahiro KajiharaDivision of Global Epidemiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
Tokiko WatanabeDepartment of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Ayato TakadaDivision of Global Epidemiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.ORCID 0000-0003-2464-6642
Hokkaido University · JPThe University of Osaka · JP

Funding

Japan Agency for Medical Research and Development JP21jm0110019Japan Society for the Promotion of Science 19K06399Japan Society for the Promotion of Science 24390110Ministry of Education, Culture, Sports, Science and Technology 16H06429Ministry of Education, Culture, Sports, Science and Technology 16H06434Ministry of Education, Culture, Sports, Science and Technology 16K21723
6 · The paper itself

Abstract

Highly pathogenic avian influenza viruses (HPAIVs) with H5 and H7 hemagglutinin (HA) subtypes are derived from their low pathogenic counterparts following the acquisition of multiple basic amino acids in their HA cleavage site. It has been suggested that consecutive adenine residues and a stem-loop structure in the viral RNA region that encodes the cleavage site are essential for the acquisition of the polybasic cleavage site. By using a reporter assay to detect non-templated nucleotide insertions, we found that insertions more frequently occurred in the RNA region (29 nucleotide-length) encoding the cleavage site of an H5 HA gene that was predicted to have a stem-loop structure containing consecutive adenines than in a mutated corresponding RNA region that had a disrupted loop structure with fewer adenines. In virus particles generated by using reverse genetics, nucleotide insertions that created additional codons for basic amino acids were found in the RNA region encoding the cleavage site of an H5 HA gene but not in the mutated RNA region. We confirmed the presence of virus clones with the ability to replicate without trypsin in a plaque assay and to cause lethal infection in chicks. These results demonstrate that the stem-loop structure containing consecutive adenines in HA genes is a key molecular determinant for the emergence of H5 HPAIVs.

Indexed as

cleavage sitehemagglutininhighly pathogenic avian influenza virusinfluenza virusnucleotide insertionRNA secondary structure

Identifiers

PMID34959552
PMCPMC8707032
OpenAlexW4200198082

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.