Abstract
Orthohantaviruses, causing hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome, pose a significant public health threat worldwide. Despite the significant mortality and morbidity, effective antiviral therapeutics for orthohantavirus infections are currently unavailable. This study aimed to investigate the prevalence of HFRS-associated orthohantaviruses and identify the etiological agent of orthohantavirus outbreaks in southern Republic of Korea (ROK). We collected small mammals on Jeju Island during 2018-2020. We detected the Hantaan virus (HTNV)-specific antibodies and RNA using an indirect immunofluorescence assay test and reverse transcription-polymerase chain reaction on Apodemus agrarius chejuensis (A. chejuensis). The prevalence of anti-HTNV antibodies among rodents was 14.1%. A total of six seropositive mouse harbored HTNV RNA. The amplicon-based next-generation sequencing provided nearly full-length tripartite genomic sequences of six HTNV harbored by A. chejuensis. Phylogenetic and tanglegram analyses were conducted for inferring evolutionary relationships between orthohantaviruses with their reservoir hosts. Phylogenetic analysis showed a novel distinct HTNV genotype. The detected HTNV genomic sequences were phylogenetically related to a viral sequence derived from HFRS patient in southern ROK. Tanglegram analysis demonstrated the segregation of HTNV genotypes corresponding to Apodemus spp. divergence. Our results suggest that A. chejuensis-borne HTNV may be a potential etiological agent of HFRS in southern ROK. Ancestral HTNV may infect A. chejuensis prior to geological isolation between the Korean peninsula and Jeju Island, supporting the co-evolution of orthohantaviruses and rodents. This study arises awareness among physicians for HFRS outbreaks in southern ROK.
Highlights
Orthohantavirus (Family Hantaviridae, Order Bunyavirales) is an enveloped negative-sense single-stranded RNA virus containing large (L), medium (M), and small (S) genome segments [1]
Our results suggest that A. chejuensis-borne Hantaan virus (HTNV) may be a potential etiological agent of hemorrhagic fever with renal syndrome (HFRS) in southern Republic of Korea (ROK)
According to the Korea Disease Control and Prevention Agency, about 18 HFRS cases have been reported over the past decade on Jeju Island, Republic of Korea (ROK)
Summary
Orthohantavirus (Family Hantaviridae, Order Bunyavirales) is an enveloped negative-sense single-stranded RNA virus containing large (L), medium (M), and small (S) genome segments [1]. Orthohantaviruses are etiological agents of hemorrhagic fever with renal syndrome (HFRS) with fatality rates of 1–15% in Eurasia [2]. Antiviral therapeutics for orthohantavirus infections remain ineffective and unavailable despite the significant mortality and morbidity of the diseases. Orthohantaviruses, causing hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome, pose a significant public health threat worldwide. Despite the significant mortality and morbidity, effective antiviral therapeutics for orthohantavirus infections are currently unavailable. This study aimed to investigate the prevalence of HFRSassociated orthohantaviruses and identify the etiological agent of orthohantavirus outbreaks in southern Republic of Korea (ROK)
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