OmniVira

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
Affiliations 12 institutions
  1. Virology Unit/National Influenza Centre, Institut Pasteur in Cambodia, Phnom Penh, Cambodia.
  2. Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
  3. Centers for Disease Control and Prevention, Atlanta, Georgia, USA Centers for Disease Control and Prevention, Phnom Penh, Cambodia.
  4. National Institute of Public Health, Phnom Penh, Cambodia.
  5. Communicable Disease Department, Ministry of Health, Phnom Penh, Cambodia.
  6. Kantha Bopha Hospital, Phnom Penh, Cambodia.
  7. Centers for Disease Control and Prevention, Atlanta, Georgia, USA Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
  8. National Veterinary Research Institute, Ministry of Agriculture, Forestry and Fisheries, Phnom Penh, Cambodia.
  9. World Health Organization, Phnom Penh, Cambodia.
  10. Food and Agriculture Organization, Phnom Penh, Cambodia.
  11. U.S. Naval Medical Research Unit No. 2, Phnom Penh, Cambodia.
  12. Virology Unit/National Influenza Centre, Institut Pasteur in Cambodia, Phnom Penh, Cambodia [email protected].
PMID25210193 DOI10.1128/JVI.01887-14 Year2014 Journal Journal of virology J Virol Languageeng Statusppublish

Abstract

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.

Supporting text Virus Host Location
Genetic Markers 3 Virus Attachment 55 Adolescent 34 Adult 71 Amino Acid Substitution 81 Cambodia 12 Child 42 Child, Preschool 37 Cluster Analysis 31 Female 289 Genotype 137 Hemagglutinin Glycoproteins, Influenza Virus 180 Humans 1440 Infant 26 Influenza A Virus, H5N1 Subtype 300 Influenza, Human 286 Male 224 Middle Aged 60 Molecular Sequence Data 160 Mutation, Missense 26 Phylogeny 805 Sequence Analysis, DNA 113

Evidence records

4 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type Viral Detection
1 records
OVE1827 Viral Detection
Key finding

Influenza A(H5N1) virus was detected in clinical specimens from human cases in Cambodia in 2013.

Virus
Influenza A virus H5N1
Host
human Homo sapiens Natural host
Location
Cambodia
Supporting text

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.

Method
molecular characterization
Sample type
clinical specimens
Geographic raw
Cambodia
Country inferred
KHM
Functional Mechanism
3 records · 2 evidence types
Evidence type Receptor Usage
1 records
OVE1828 Receptor Usage
Key finding

Mutations K189R and Q222L in influenza A(H5N1) were associated with altered receptor-binding specificity in viruses from human cases in Cambodia.

Virus
Influenza A virus H5N1
Host
human Homo sapiens Natural host
Location
Not specified
Supporting text

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).

Method
molecular characterization
Receptors
sialic acid receptor
Evidence type Molecular Adaptation
2 records
OVE1829 Molecular Adaptation
Key finding

Influenza A(H5N1) viruses from human cases in Cambodia carried mutations N220K and Q222L that together were associated with respiratory droplet transmission in ferrets.

Virus
Influenza A virus H5N1
Host
Not specified
Location
Not specified
Supporting text

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
Receptors
receptor-binding specificity
Mutations
K189R | Q222L | N220K
Mechanism types
receptor binding | transmission fitness
OVE1830 Molecular Adaptation
Key finding

Human infections with influenza A(H5N1) virus in Cambodia showed mutations absent from poultry and environmental samples, supporting an animal-to-human spillover followed by limited adaptation in humans.

Virus
Influenza A virus H5N1
Host
birds Aves Natural host human Homo sapiens Natural host
Location
Cambodia
Supporting text

Human infections with influenza A(H5N1) virus in Cambodia increased sharply during 2013. 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.

Mechanism types
host tropism | host adaptation | adaptive mutation