title: Direct whole-genome deep-sequencing of human  respiratory syncytial virus A and B from  Vietnamese children identifies distinct patterns  of inter- and intra-host evolution.
abstract: Human respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in children ,2 years of age. Little is known about RSV intra-host genetic diversity over the course of infection or about the immune pressures that drive RSV molecular evolution. We performed whole-genome deep-sequencing on 53 RSV-positive samples (37 RSV subgroup A and 16 RSV subgroup B) collected from the upper airways of hospitalized children in southern Vietnam over two consecutive seasons. RSV A NA1 and RSV B BA9 were the predominant genotypes found in our samples, consistent with other reports on global RSV circulation during the same period. For both RSV A and B, the M gene was the most conserved, confirming its potential as a target for novel therapeutics. The G gene was the most variable and was the only gene under detectable positive selection. Further, positively selected sites inG were found in close proximity to and in some cases overlapped with predicted glycosylation motifs, suggesting that selection on amino acid glycosylation may drive viral genetic diversity. We further identified hotspots and coldspots of intra-host genetic diversity in the RSV genome, some of which may highlight previously unknown regions of functional importance.
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Ho Chi Minh City, Vietnam.
authors.forename: Lien Anh Ha
authors.initials: LAH
authors.lastname: Do
authors.affiliation: Genome Institute of Singapore, Genome Building, 138672 Singapore.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wilm
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Ho Chi Minh City, Vietnam.|Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
authors.forename: H Rogier
authors.initials: HR
authors.lastname: van Doorn
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Ho Chi Minh City, Vietnam.
authors.forename: Ha Minh
authors.initials: HM
authors.lastname: Lam
authors.affiliation: Genome Institute of Singapore, Genome Building, 138672 Singapore.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Sim
authors.affiliation: Genome Institute of Singapore, Genome Building, 138672 Singapore.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Sukumaran
authors.affiliation: Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam.
authors.forename: Anh Tuan
authors.initials: AT
authors.lastname: Tran
authors.affiliation: Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam.
authors.forename: Bach Hue
authors.initials: BH
authors.lastname: Nguyen
authors.affiliation: Children's Hospital 2, Ben Nghe Ward, District 1, Ho Chi Minh City, Vietnam.
authors.forename: Thi Thu Loan
authors.initials: TTL
authors.lastname: Tran
authors.affiliation: Children's Hospital 2, Ben Nghe Ward, District 1, Ho Chi Minh City, Vietnam.
authors.forename: Quynh Huong
authors.initials: QH
authors.lastname: Tran
authors.affiliation: Children's Hospital 2, Ben Nghe Ward, District 1, Ho Chi Minh City, Vietnam.
authors.forename: Quoc Bao
authors.initials: QB
authors.lastname: Vo
authors.affiliation: Children's Hospital 2, Ben Nghe Ward, District 1, Ho Chi Minh City, Vietnam.
authors.forename: Nguyen Anh Tran
authors.initials: NAT
authors.lastname: Dac
authors.affiliation: Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam.
authors.forename: Hong Nhien
authors.initials: HN
authors.lastname: Trinh
authors.affiliation: Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam.
authors.forename: Thi Thanh Hai
authors.initials: TTH
authors.lastname: Nguyen
authors.affiliation: Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam.
authors.forename: Bao Tinh Le
authors.initials: BTL
authors.lastname: Binh
authors.affiliation: Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam.
authors.forename: Khanh
authors.initials: K
authors.lastname: Le
authors.affiliation: Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam.
authors.forename: Minh Tien
authors.initials: MT
authors.lastname: Nguyen
authors.affiliation: Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam.
authors.forename: Quang Tung
authors.initials: QT
authors.lastname: Thai
authors.affiliation: Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam.
authors.forename: Thanh Vu
authors.initials: TV
authors.lastname: Vo
authors.affiliation: Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam.
authors.forename: Ngoc Quang Minh
authors.initials: NQM
authors.lastname: Ngo
authors.affiliation: Children's Hospital 2, Ben Nghe Ward, District 1, Ho Chi Minh City, Vietnam.
authors.forename: Thi Kim Huyen
authors.initials: TKH
authors.lastname: Dang
authors.affiliation: Children's Hospital 2, Ben Nghe Ward, District 1, Ho Chi Minh City, Vietnam.
authors.forename: Ngoc Huong
authors.initials: NH
authors.lastname: Cao
authors.affiliation: Children's Hospital 2, Ben Nghe Ward, District 1, Ho Chi Minh City, Vietnam.
authors.forename: Thu Van
authors.initials: TV
authors.lastname: Tran
authors.affiliation: Children's Hospital 2, Ben Nghe Ward, District 1, Ho Chi Minh City, Vietnam.
authors.forename: Lu Viet
authors.initials: LV
authors.lastname: Ho
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Ho Chi Minh City, Vietnam.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Ho Chi Minh City, Vietnam.|Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.|Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Menno
authors.initials: M
authors.lastname: de Jong
authors.affiliation: Genome Institute of Singapore, Genome Building, 138672 Singapore.
authors.forename: Swaine
authors.initials: S
authors.lastname: Chen
authors.affiliation: Genome Institute of Singapore, Genome Building, 138672 Singapore.
authors.forename: Niranjan
authors.initials: N
authors.lastname: Nagarajan
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Ho Chi Minh City, Vietnam.|Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
authors.forename: Juliet E
authors.initials: JE
authors.lastname: Bryant
authors.affiliation: Genome Institute of Singapore, Genome Building, 138672 Singapore.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hibberd
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D019143:Evolution, Molecular; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D014644:Genetic Variation; D016679:Genome, Viral / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008958:Models, Molecular; D010802:Phylogeny; D011487:Protein Conformation; D018357:Respiratory Syncytial Virus Infections / Q000453:epidemiology; D018113:Respiratory Syncytial Virus, Human / Q000145:classification* / Q000235:genetics*; D014744:Vietnam / Q000453:epidemiology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D014764:Viral Proteins