Urinary genome detection and tracking of Hantaan virus from hemorrhagic fever with renal syndrome patients using multiplex PCR-based next-generation sequencing.

Seungchan Cho,Geum-Young Lee,Seung-Ho Lee,Jin-Won Song,Jin Sun No,Kyungmin Park,Dong Hyun Song,Jingyeong Lee,Won-Keun Kim,Se Hun Gu,Jeong-Ah Kim,Seong Tae Jeong,Daesang Lee,Hayne Cho Park,Jongwoo Kim,Yongjin Yi,Jaehun Jung,Michael R Holbrook

doi:10.1371/journal.pntd.0009707

Abstract

BackgroundHantavirus infection occurs through the inhalation of aerosolized excreta, including urine, feces, and saliva of infected rodents. The presence of Hantaan virus (HTNV) RNA or infectious particles in urine specimens of patient with hemorrhagic fever with renal syndrome (HFRS) remains to be investigated.Methodology/Principal findingsWe collected four urine and serum specimens of Republic of Korea Army (ROKA) patients with HFRS. We performed multiplex PCR-based next-generation sequencing (NGS) to obtain the genome sequences of clinical HTNV in urine specimens containing ultra-low amounts of viral genomes. The epidemiological and phylogenetic analyses of HTNV demonstrated geographically homogenous clustering with those in Apodemus agrarius captured in highly endemic areas, indicating that phylogeographic tracing of HTNV genomes reveals the potential infection sites of patients with HFRS. Genetic exchange analyses showed a genetic configuration compatible with HTNV L segment exchange in nature.Conclusion/SignificanceOur results suggest that whole or partial genome sequences of HTNV from the urine enabled to track the putative infection sites of patients with HFRS by phylogeographically linking to the zoonotic HTNV from the reservoir host captured at endemic regions. This report raises awareness among physicians for the presence of HTNV in the urine of patients with HFRS.

Highlights

Hantaviruses are enveloped negative-sense, single-stranded tripartite RNA viruses, consisting of large (L), medium (M), and small (S) segments [1]
Our results suggest that whole or partial genome sequences of Hantaan virus (HTNV) from the urine enabled to track the putative infection sites of patients with hemorrhagic fever with renal syndrome (HFRS) by phylogeographically
Hantavirus transmission to humans occurs via inhalation of aerosolized excreta, including urine, feces, and saliva of infected rodents

Summary

Introduction

Hantaviruses (genus Orthohantavirus, family Hantaviridae, and order Bunyavirales) are enveloped negative-sense, single-stranded tripartite RNA viruses, consisting of large (L), medium (M), and small (S) segments [1]. Hantavirus infections cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome in humans. Hantavirus transmission to humans occurs via inhalation of aerosolized excreta, including urine, feces, and saliva of infected rodents. The clinical course of HFRS typically defines five phases: febrile, hypotensive, oliguric, diuretic, and convalescent [4]. The oliguric phase indicates renal dysfunction, hypervolemia, and blood electrolyte imbalance, lasting three to seven days. The convalescent phase is a recovery stage that lasts three to six months, and is marked by progressive improvements in glomerular filtration rate, renal blood flow, and urine output control. Hantavirus infection occurs through the inhalation of aerosolized excreta, including urine, feces, and saliva of infected rodents. The presence of Hantaan virus (HTNV) RNA or infectious particles in urine specimens of patient with hemorrhagic fever with renal syndrome (HFRS) remains to be investigated

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Discussion

Conclusion