A once-obscure group of rodent-borne viruses, known to cause hemorrhagic fever with renal syndrome (HFRS), gained immediate notoriety in the spring of 1993, when an outbreak of a rapidly progressive cardiopulmonary disease erupted in the Four Corners region of the southwestern United States. That a hantavirus, harbored by a neotomine rodent species identified as a reservoir host a decade earlier, would be responsible for this frequently fatal respiratory disease, now known as hantavirus pulmonary syndrome (HPS), was beyond the collective imagination of clinicians, epidemiologists and medical virologists. The realization that rodent-borne hantaviruses are capable of causing diseases as clinically disparate as HFRS and HPS raises the probability that hantaviruses recently detected in shrews would similarly cause a wide spectrum of disease. In-depth studies on the transmission dynamics and infectivity of Imjin virus (MJNV), recently isolated from the Ussuri shrew (Crocidura lasiura) in South Korea, may provide clues about its pathogenicity, as well as useful reagents to more rapidly diagnose future outbreaks of newly recognized diseases caused by emerging hantaviruses. The primary objectives of the proposed research are to determine the intraspecies transmission of MJNV and to ascertain its importance to human health and disease. Our central hypothesis is that MJNV is the prototype of a large clade of shrew-borne hantaviruses, which have co-evolved with their reservoir hosts and which are capable of causing infection, and possibly disease, in humans. Our experimental plan employs serological and molecular biological techniques for the detection and characterization of this new hantavirus and for the demonstration of human infection.
Specific Aim 1. To determine the antigenic, genetic and phylogenetic relationships between MJNV and other hantaviruses.
Specific Aim 2. To determine the host range, temporal occurrence and spatial distribution of MJNV infection.
Specific Aim 3. To determine the infectivity and disease potential of MJNV in humans. The proposed research is innovative in that it challenges the long-held dogma that rodents are the sole reservoir hosts of hantaviruses. Newfound information about the evolutionary origin, host range and disease potential of MJNV will provide insights into the complex co-evolutionary history and host-parasite relationship of hantaviruses, which may lead ultimately to identifying the molecular determinants of hantavirus pathogenicity and tissue targeting.

Public Health Relevance

Carried by many species of rodents worldwide, hantaviruses are medically important viruses, which cause two distinct diseases in humans. One is a type of hemorrhagic fever with associated kidney failure occurring in Europe and Asia and the other is a rapidly progressive, frequently fatal respiratory disease occurring in the Americas. Recently, a new group of hantaviruses have been discovered in shrews. Because of their relatedness to disease-causing hantaviruses, the proposed research aims to determine if these newly identified hantaviruses cause infection and disease in humans. New knowledge about the shrew-borne hantaviruses will better prepare us to diagnose future outbreaks of hantavirus diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI075057-04
Application #
8121416
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Cassetti, Cristina
Project Start
2008-08-08
Project End
2014-07-31
Budget Start
2011-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2011
Total Cost
$349,356
Indirect Cost
Name
University of Hawaii
Department
Pediatrics
Type
Schools of Medicine
DUNS #
965088057
City
Honolulu
State
HI
Country
United States
Zip Code
96822
Gu, Se Hun; Kumar, Mukesh; Sikorska, Beata et al. (2016) Isolation and partial characterization of a highly divergent lineage of hantavirus from the European mole (Talpa europaea). Sci Rep 6:21119
Arai, Satoru; Kang, Hae Ji; Gu, Se Hun et al. (2016) Genetic Diversity of Artybash Virus in the Laxmann's Shrew (Sorex caecutiens). Vector Borne Zoonotic Dis 16:468-75
Gu, Se Hun; Arai, Satoru; Yu, Hon-Tsen et al. (2016) Genetic variants of Cao Bang hantavirus in the Chinese mole shrew (Anourosorex squamipes) and Taiwanese mole shrew (Anourosorex yamashinai). Infect Genet Evol 40:113-8
Kang, Hae Ji; Gu, Se Hun; Cook, Joseph A et al. (2016) Dahonggou Creek virus, a divergent lineage of hantavirus harbored by the long-tailed mole (Scaptonyx fusicaudus). Trop Med Health 44:16
Yashina, Liudmila N; Abramov, Sergey A; Dupal, Tamara A et al. (2015) Hokkaido genotype of Puumala virus in the grey red-backed vole (Myodes rufocanus) and northern red-backed vole (Myodes rutilus) in Siberia. Infect Genet Evol 33:304-13
Gu, Se Hun; Hejduk, Janusz; Markowski, Janusz et al. (2015) Whole-Genome Sequence of a Novel Hantavirus Isolated from the European Mole (Talpa europaea). Genome Announc 3:
Gu, Se Hun; Kim, Young-Sik; Baek, Luck Ju et al. (2015) Lethal disease in infant and juvenile Syrian hamsters experimentally infected with Imjin virus, a newfound crocidurine shrew-borne hantavirus. Infect Genet Evol 36:231-239
Kang, Hae Ji; Stanley, William T; Esselstyn, Jacob A et al. (2014) Expanded host diversity and geographic distribution of hantaviruses in sub-Saharan Africa. J Virol 88:7663-7
Gu, Se Hun; Lim, Burton K; Kadjo, Blaise et al. (2014) Molecular phylogeny of hantaviruses harbored by insectivorous bats in Côte d'Ivoire and Vietnam. Viruses 6:1897-910
Gu, Se Hun; Hejduk, Janusz; Markowski, Janusz et al. (2014) Co-circulation of soricid- and talpid-borne hantaviruses in Poland. Infect Genet Evol 28:296-303

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