title: Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing.
abstract: Emerging and re-emerging infectious diseases caused by RNA viruses pose a critical public health threat. Next generation sequencing (NGS) is a powerful technology to define genomic sequences of the viruses. Of particular interest is the use of whole genome sequencing (WGS) to perform phylogeographic analysis, that allows the detection and tracking of the emergence of viral infections. Hantaviruses, Bunyaviridae, cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans. We propose to use WGS for the phylogeographic analysis of human hantavirus infections. A novel multiplex PCR-based NGS was developed to gather whole genome sequences of Hantaan virus (HTNV) from HFRS patients and rodent hosts in endemic areas. The obtained genomes were described for the spatial and temporal links between cases and their sources. Phylogenetic analyses demonstrated geographic clustering of HTNV strains from clinical specimens with the HTNV strains circulating in rodents, suggesting the most likely site and time of infection. Recombination analysis demonstrated a genome organization compatible with recombination of the HTNV S segment. The multiplex PCR-based NGS is useful and robust to acquire viral genomic sequences and may provide important ways to define the phylogeographical association and molecular evolution of hantaviruses.
authors.affiliation: Department of Microbiology, College of Medicine, Korea University, Seoul, 02841, Republic of Korea.
authors.forename: Won-Keun
authors.initials: WK
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Medicine, Korea University, Seoul, 02841, Republic of Korea.
authors.forename: Jeong-Ah
authors.initials: JA
authors.lastname: Kim
authors.affiliation: The 5th R&D Institute, Agency for Defense Development, Yuseong P.O. Box 35, Daejeon, 34186, Republic of Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Song
authors.affiliation: The 5th R&D Institute, Agency for Defense Development, Yuseong P.O. Box 35, Daejeon, 34186, Republic of Korea.
authors.forename: Daesang
authors.initials: D
authors.lastname: Lee
authors.affiliation: The Armed Forces Medical Center, Saemaeul-ro, 177 beon-gil, Seongnam-si, Gyeonggi-do, 13574, Republic of Korea.
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Medicine, Korea University, Seoul, 02841, Republic of Korea.
authors.forename: Sook-Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Microbiology, College of Medicine, Korea University, Seoul, 02841, Republic of Korea.
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Microbiology, College of Medicine, Korea University, Seoul, 02841, Republic of Korea.
authors.forename: Jin Sun
authors.initials: JS
authors.lastname: No
authors.affiliation: Department of Microbiology, College of Medicine, Korea University, Seoul, 02841, Republic of Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Medicine, Korea University, Seoul, 02841, Republic of Korea.
authors.forename: Jeong Hoon
authors.initials: JH
authors.lastname: Kho
authors.affiliation: The 5th R&D Institute, Agency for Defense Development, Yuseong P.O. Box 35, Daejeon, 34186, Republic of Korea.
authors.forename: Se Hun
authors.initials: SH
authors.lastname: Gu
authors.affiliation: The 5th R&D Institute, Agency for Defense Development, Yuseong P.O. Box 35, Daejeon, 34186, Republic of Korea.
authors.forename: Seong Tae
authors.initials: ST
authors.lastname: Jeong
authors.affiliation: The Center for Genome Science, US Army Medical Research Institute of Infectious Disease at Fort Detrick, MD, 21702, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wiley
authors.affiliation: 5th Medical Detachment, 168th Multifunctional Medical Battalion, 65th Medical Brigade, Unit 15247, APO AP 96205-5247, United States of America.
authors.forename: Heung-Chul
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Public Health Command District-Korea (Provisional), 65th Medical Brigade, Unit 15281, APO AP 96205-5281, United States of America.
authors.forename: Terry A
authors.initials: TA
authors.lastname: Klein
authors.affiliation: The Center for Genome Science, US Army Medical Research Institute of Infectious Disease at Fort Detrick, MD, 21702, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Palacios
authors.affiliation: Department of Microbiology, College of Medicine, Korea University, Seoul, 02841, Republic of Korea.
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Song
mesh_terms: D000818:Animals; D021821:Communicable Diseases, Emerging; D018063:Hantaan virus / Q000502:physiology*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000453:epidemiology / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D010802:Phylogeny; D058974:Phylogeography; D012367:RNA, Viral / Q000235:genetics*; D011995:Recombination, Genetic; D056910:Republic of Korea / Q000453:epidemiology; D012377:Rodentia
chemical_list: D012367:RNA, Viral