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 Rith; C Todd Davis; Veasna Duong; Borann Sar; Srey Viseth Horm; Savuth Chin; Sovann Ly; Denis Laurent; Beat Richner; Ikwo Oboho; Yunho Jang; William Davis; Sharmi Thor; Amanda Balish; A Danielle Iuliano; San Sorn; Davun Holl; Touch Sok; Heng Seng; Arnaud Tarantola; Reiko Tsuyuoka; Amy Parry; Nora Chea; Lotfi Allal; Paul Kitsutani; Dora Warren; Michael Prouty; Paul Horwood; Marc-Alain Widdowson; Stephen Lindstrom; Julie Villanueva; Ruben Donis; Nancy Cox; Philippe Buchy

doi:10.1128/JVI.01887-14

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

J Virol. 2014 Dec;88(23):13897-909. doi: 10.1128/JVI.01887-14. Epub 2014 Sep 10.

Authors

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

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].

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Adolescent
Adult
Amino Acid Substitution
Cambodia
Child
Child, Preschool
Cluster Analysis
Female
Genetic Markers*
Genotype
Hemagglutinin Glycoproteins, Influenza Virus / genetics
Humans
Infant
Influenza A Virus, H5N1 Subtype / genetics*
Influenza A Virus, H5N1 Subtype / isolation & purification
Influenza A Virus, H5N1 Subtype / physiology*
Influenza, Human / virology*
Male
Middle Aged
Molecular Sequence Data
Mutation, Missense
Phylogeny
Sequence Analysis, DNA
Virus Attachment*

Substances

Genetic Markers
Hemagglutinin Glycoproteins, Influenza Virus

Grants and funding

001/WHO_/World Health Organization/International