JVI Accepted Manuscript Posted Online 1 July 2015 J. Virol. doi:10.1128/JVI.00708-15 Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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Manuscript for publication as a short-form paper in the Journal of Virology

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Evolution of influenza B virus in Kuala Lumpur, Malaysia between 1995

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and 2008

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Running title: Influenza B virus in Kuala Lumpur, Malaysia

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I-Ching Sam,a,b,1# Yvonne C. F. Su,c,1 Yoke Fun Chan,a Siti Sarah Nor'E,d Ardalinah Hassan,a

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Faizatul Lela Jafar,a Udayan Joseph,c Rebecca A. Halpin,e Elodie Ghedin,f Poh Sim Hooi,b

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Mathieu Fourment,g* Hamimah Hassan,a Sazaly AbuBakar,d David E. Wentworth,e† Gavin J.

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D. Smithc,g#

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Department of Medical Microbiology, Faculty of Medicine, University Malaya, 50603 Kuala

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Lumpur, Malaysiaa; Diagnostic Virology Laboratory, University Malaya Medical Centre,

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59100 Kuala Lumpur, Malaysiab; Duke-NUS Graduate Medical School, 8 College Road,

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Singapore 169857c; Tropical Infectious Diseases Research and Education Centre, University

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Malaya, 50603 Kuala Lumpur, Malaysiad; J. Craig Venter Institute, 9704 Medical Center

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Drive, Rockville, MD 20850, USAe; Department of Biology, Center for Genomics & Systems

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Biology, and Global Institute of Public Health, New York University, New York, NY 10003,

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USAf; Duke Global Health Institute, Duke University, Durham, North Carolina, USAg

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* Present address: Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles

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Perkins Centre, School of Biological Sciences and Sydney Medical School, The University of

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Sydney, Sydney, NSW 2006, Australia

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Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Rd, NE,

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Atlanta, GA 30333, USA

Present address: David E. Wentworth, Virology Surveillance and Diagnosis Branch,

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I.C.S. and Y.C.F.S contributed equally to this work.

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#

To whom correspondence should be addressed: [email protected] and

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[email protected]

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Manuscript information: 75 words in the abstract, 1,301 words in the main text.

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Abstract

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Influenza B virus causes significant disease but remains understudied in tropical regions. We

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sequenced 72 influenza B viruses collected in Kuala Lumpur, Malaysia from 1995–2008. The

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predominant circulating lineage (Victoria or Yamagata) changed every 1–3 years, and these

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shifts were associated with increased incidence of influenza B. We also found poor lineage

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matches with recommended influenza vaccine strains. While most influenza B lineages in

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Malaysia were short-lived, one circulated for 3–4 years.

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TEXT

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Influenza B virus causes seasonal epidemics and a significant disease burden in humans, with

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reported rates of up to 82% of total influenza cases around the world, and 22-44% of

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influenza-related child deaths in the USA (1). Since the mid-1970s, influenza B has formed

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two antigenically distinct lineages “B/Victoria/2/87-like” and “B/Yamagata/16/88-like”,

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referred to as the Victoria and Yamagata lineages, respectively (2). Although the two lineages

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co-circulate in humans, Dhanasekaran et al. (3) recently demonstrated significant

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evolutionary and epidemiological differences between the two lineages. The Victoria lineage

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is subject to stronger seasonal bottlenecks, higher transmission rates, greater antigenic

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variation, stronger positive selection and mostly infects younger age groups. In contrast, the

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Yamagata lineage experiences less severe bottlenecks and infects older people (3). In tropical

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Kuala Lumpur in Malaysia, there is year-round influenza activity with biannual epidemics in

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May–July and November–January (4). A retrospective epidemiological study of hospitalized

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children in Kuala Lumpur from 1982–2008 found that 297 of 2,708 (11%) patients with

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confirmed respiratory virus infection were positive for influenza, making it the third most

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common respiratory virus affecting children

Evolution of Influenza B Virus in Kuala Lumpur, Malaysia, between 1995 and 2008.

Influenza B virus causes significant disease but remains understudied in tropical regions. We sequenced 72 influenza B viruses collected in Kuala Lump...
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