AUTHOR=Kim Won-Keun , Cho Seungchan , Lee Seung-Ho , No Jin Sun , Lee Geum-Young , Park Kyungmin , Lee Daesang , Jeong Seong Tae , Song Jin-Won TITLE=Genomic Epidemiology and Active Surveillance to Investigate Outbreaks of Hantaviruses JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=Volume 10 - 2020 YEAR=2021 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.532388 DOI=10.3389/fcimb.2020.532388 ISSN=2235-2988 ABSTRACT=Emerging and re-emerging RNA viruses pose significant public health, economic, and societal burdens. Viral genome tracking has recently been utilized to rapidly and precisely characterize an outbreak from emerging virus origin. Here, we introduce genomic epidemiology and active surveillance for the emergence of zoonotic RNA viruses, e.g. Orthohantavirus, Ebola virus, Lassa virus, and Zika virus, based on viral genomic sequences obtained from patients and natural reservoirs. Orthohantaviruses (family Hantaviridae, order Bunyavirales), which are enveloped negative-sense single-stranded RNA viruses, are emerging zoonotic pathogens harbored by small mammal hosts, including rodents, bats, moles, and shrews. Orthohantavirus infections cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome in humans. Active surveillance of HFRS patients was characterized 1) by recovering whole-genome sequences of Hantaan virus (HTNV) using amplicon (multiplex PCR-based) next-generation sequencing, 2) by tracing the putative infection site of a patient using an epidemiological questionnaire, and 3) by collecting HTNV-positive rodents using targeted rodent trapping. The active targeted surveillance elicited high-resolution phylogeographic links of patient- and rodent-derived orthohantavirus genome sequences, identifying the infection source by temporally and spatially tracking viral genomes. This review highlights the recent studies of tracking viral genomes for identifying and characterizing emerging virus outbreaks worldwide. Active surveillance provides an effective modus operandi for identifying rodent-borne orthohantavirus infection sites. Thus, this report provides insights into necessity of preemptive epidemiological survey, responsiveness, and preparedness to emerging virus outbreaks.