Identification of molecular markers associated with alteration of receptor-binding specificity in a novel genotype of highly pathogenic avian influenza A(H5N1) viruses detected in Cambodia in 2013.
Sareth Rith1
C Todd Davis2
Veasna Duong1
Borann Sar3
Srey Viseth Horm1
Savuth Chin4
Sovann Ly5
Denis Laurent6
Beat Richner6
Ikwo Oboho7
Yunho Jang2
William Davis2
Sharmi Thor2
Amanda Balish2
A Danielle Iuliano2
San Sorn8
Davun Holl8
Touch Sok5
Heng Seng5
Arnaud Tarantola1
Reiko Tsuyuoka9
Amy Parry9
Nora Chea9
Lotfi Allal10
Paul Kitsutani3
Dora Warren3
Michael Prouty11
Paul Horwood1
Marc-Alain Widdowson2
Stephen Lindstrom2
Julie Villanueva2
Ruben Donis2
Nancy Cox2
Philippe Buchy12
Affiliations12 institutions
Virology Unit/National Influenza Centre, Institut Pasteur in Cambodia, Phnom Penh, Cambodia.
Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Centers for Disease Control and Prevention, Atlanta, Georgia, USA Centers for Disease Control and Prevention, Phnom Penh, Cambodia.
National Institute of Public Health, Phnom Penh, Cambodia.
Communicable Disease Department, Ministry of Health, Phnom Penh, Cambodia.
Kantha Bopha Hospital, Phnom Penh, Cambodia.
Centers for Disease Control and Prevention, Atlanta, Georgia, USA Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
National Veterinary Research Institute, Ministry of Agriculture, Forestry and Fisheries, Phnom Penh, Cambodia.
World Health Organization, Phnom Penh, Cambodia.
Food and Agriculture Organization, Phnom Penh, Cambodia.
U.S. Naval Medical Research Unit No. 2, Phnom Penh, Cambodia.
Virology Unit/National Influenza Centre, Institut Pasteur in Cambodia, Phnom Penh, Cambodia [email protected].
Human infections with influenza A(H5N1) virus in Cambodia increased sharply during 2013. Molecular characterization of viruses detected in clinical specimens from human cases revealed the presence of mutations associated with the alteration of receptor-binding specificity (K189R, Q222L) and respiratory droplet transmission in ferrets (N220K with Q222L). Discovery of quasispecies at position 222 (Q/L), in addition to the absence of the mutations in poultry/environmental samples, suggested that the mutations occurred during human infection and did not transmit further.
Genomic and phylogenetic analyses of H5N1 viruses in Cambodian human infections identified mutations in the hemagglutinin gene (K189R, N220K, Q222L) that arose during human infection and altered receptor-binding specificity.
Molecular characterization of viruses detected in clinical specimens from human cases revealed the presence of mutations associated with the alteration of receptor-binding specificity (K189R, Q222L) and respiratory droplet transmission in ferrets (N220K with Q222L)... MeSH terms include 'Phylogeny' and 'Sequence Analysis, DNA'.
Genes or proteins
hemagglutinin
Analysis methods
phylogenetic analysis; sequence analysis
Molecular Adaptation1 records
Molecular AdaptationExtraction confidence 0.95
Key finding
Mutations K189R, N220K, and Q222L in H5N1 hemagglutinin were linked to altered receptor-binding specificity and may have arisen during human infection.
Molecular characterization of viruses detected in clinical specimens from human cases revealed the presence of mutations associated with the alteration of receptor-binding specificity (K189R, Q222L) and respiratory droplet transmission in ferrets (N220K with Q222L).
Genes or proteins
Hemagglutinin Glycoproteins
Receptors
Virus Attachment
Mutations
K189R; N220K; Q222L
Mechanism types
receptor_binding; transmission_fitness
Receptor Usage1 records
Receptor UsageExtraction confidence 0.90
Key finding
Mutations K189R and Q222L in the hemagglutinin of avian influenza A(H5N1) viruses detected in Cambodian human cases altered receptor-binding specificity.
Molecular characterization of viruses detected in clinical specimens from human cases revealed the presence of mutations associated with the alteration of receptor-binding specificity (K189R, Q222L) and respiratory droplet transmission in ferrets (N220K with Q222L).
Receptors
receptor-binding specificity
Spillover Event1 records
Spillover EventExtraction confidence 0.85
Key finding
Human cases of avian influenza A(H5N1) infection occurred in Cambodia in 2013, consistent with avian-to-human spillover.
Glycosylation at 158N of the hemagglutinin protein and receptor binding specificity synergistically affect the antigenicity and immunogenicity of a live attenuated H5N1 A/Vietnam/1203/2004 vaccine virus in ferrets.
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2009. Single mutation at the amino acid position 627 of PB2 that leads to increased virulence of an H5N1 avian influenza virus during adaptation in mice can be compensated by multiple mutations at other sites of PB2
