Three asymptomatic animal infection models of hemorrhagic fever with renal syndrome caused by hantaviruses
Abstract
Hantaan virus (HTNV) and Puumala virus (PUUV) are rodent-borne hantaviruses that are the primary causes of hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia. The development of well characterized animal models of HTNV and PUUV infection is critical for the evaluation and the potential licensure of HFRS vaccines and therapeutics. In this study we present three animal models of HTNV infection (hamster, ferret and marmoset), and two animal models of PUUV infection (hamster, ferret). Infection of hamsters with a ~3 times the infectious dose 99% (ID99) of HTNV by the intramuscular and ~1 ID99 of HTNV by the intranasal route leads to a persistent asymptomatic infection, characterized by sporadic viremia and high levels of viral genome in the lung, brain and kidney. In contrast, infection of hamsters with ~2 ID99 of PUUV by the intramuscular or ~1 ID99 of PUUV by the intranasal route leads to seroconversion with no detectable viremia, and a transient detection of viral genome. Infection of ferrets with a high dose of either HTNV or PUUV by the intramuscular route leads to seroconversion and gradual weight loss, though kidney function remained unimpaired and serum viremia and viral dissemination to organs was not detected. Inmore »
- Publication Date:
- Research Org.:
- Oak Ridge Associated Univ., Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1511899
- Alternate Identifier(s):
- OSTI ID: 1627882
- Grant/Contract Number:
- SC0014664
- Resource Type:
- Published Article
- Journal Name:
- PLoS ONE
- Additional Journal Information:
- Journal Name: PLoS ONE Journal Volume: 14 Journal Issue: 5; Journal ID: ISSN 1932-6203
- Publisher:
- Public Library of Science
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; Science & Technology - Other Topics
Citation Formats
Perley, Casey C., Brocato, Rebecca L., Kwilas, Steven A., Daye, Sharon, Moreau, Alicia, Nichols, Donald K., Wetzel, Kelly S., Shamblin, Joshua, Hooper, Jay W., and Freiberg, ed., Alexander N. Three asymptomatic animal infection models of hemorrhagic fever with renal syndrome caused by hantaviruses. United States: N. p., 2019.
Web. doi:10.1371/journal.pone.0216700.
Perley, Casey C., Brocato, Rebecca L., Kwilas, Steven A., Daye, Sharon, Moreau, Alicia, Nichols, Donald K., Wetzel, Kelly S., Shamblin, Joshua, Hooper, Jay W., & Freiberg, ed., Alexander N. Three asymptomatic animal infection models of hemorrhagic fever with renal syndrome caused by hantaviruses. United States. https://doi.org/10.1371/journal.pone.0216700
Perley, Casey C., Brocato, Rebecca L., Kwilas, Steven A., Daye, Sharon, Moreau, Alicia, Nichols, Donald K., Wetzel, Kelly S., Shamblin, Joshua, Hooper, Jay W., and Freiberg, ed., Alexander N. Fri .
"Three asymptomatic animal infection models of hemorrhagic fever with renal syndrome caused by hantaviruses". United States. https://doi.org/10.1371/journal.pone.0216700.
@article{osti_1511899,
title = {Three asymptomatic animal infection models of hemorrhagic fever with renal syndrome caused by hantaviruses},
author = {Perley, Casey C. and Brocato, Rebecca L. and Kwilas, Steven A. and Daye, Sharon and Moreau, Alicia and Nichols, Donald K. and Wetzel, Kelly S. and Shamblin, Joshua and Hooper, Jay W. and Freiberg, ed., Alexander N.},
abstractNote = {Hantaan virus (HTNV) and Puumala virus (PUUV) are rodent-borne hantaviruses that are the primary causes of hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia. The development of well characterized animal models of HTNV and PUUV infection is critical for the evaluation and the potential licensure of HFRS vaccines and therapeutics. In this study we present three animal models of HTNV infection (hamster, ferret and marmoset), and two animal models of PUUV infection (hamster, ferret). Infection of hamsters with a ~3 times the infectious dose 99% (ID99) of HTNV by the intramuscular and ~1 ID99 of HTNV by the intranasal route leads to a persistent asymptomatic infection, characterized by sporadic viremia and high levels of viral genome in the lung, brain and kidney. In contrast, infection of hamsters with ~2 ID99 of PUUV by the intramuscular or ~1 ID99 of PUUV by the intranasal route leads to seroconversion with no detectable viremia, and a transient detection of viral genome. Infection of ferrets with a high dose of either HTNV or PUUV by the intramuscular route leads to seroconversion and gradual weight loss, though kidney function remained unimpaired and serum viremia and viral dissemination to organs was not detected. In marmosets a 1,000 PFU HTNV intramuscular challenge led to robust seroconversion and neutralizing antibody production. Similarly to the ferret model of HTNV infection, no renal impairment, serum viremia or viral dissemination to organs was detected in marmosets. This is the first report of hantavirus infection in ferrets and marmosets.},
doi = {10.1371/journal.pone.0216700},
journal = {PLoS ONE},
number = 5,
volume = 14,
place = {United States},
year = {Fri May 10 00:00:00 EDT 2019},
month = {Fri May 10 00:00:00 EDT 2019}
}
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Cited by: 11 works
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Figures / Tables:
Fig 1: HTNV and PUUV infect hamsters in a dose dependent manner. Syrian hamsters were challenged with varying concentrations of either HTNV (A) or PUUV (B) through the i.m. (left) or i.n. (right) route. Between 28 and 35 days post infection hamsters were terminally bled and N-ELISA endpoint titers (log10)more »
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Works referenced in this record:
DNA Vaccination with the Hantaan Virus M Gene Protects Hamsters against Three of Four HFRS Hantaviruses and Elicits a High-Titer Neutralizing Antibody Response in Rhesus Monkeys
journal, September 2001
- Hooper, J. W.; Custer, D. M.; Thompson, E.
- Journal of Virology, Vol. 75, Issue 18
Comprehensive Multiplex One-Step Real-Time TaqMan qRT-PCR Assays for Detection and Quantification of Hemorrhagic Fever Viruses
journal, April 2014
- Pang, Zheng; Li, Aqian; Li, Jiandong
- PLoS ONE, Vol. 9, Issue 4
Isolation of the Etiologic Agent of Korean Hemorrhagic Fever
journal, March 1978
- Lee, H. W.; Lee, P. W.; Johnson, K. M.
- Journal of Infectious Diseases, Vol. 137, Issue 3
Gastrointestinal Tract As Entry Route for Hantavirus Infection
journal, September 2017
- Witkowski, Peter T.; Perley, Casey C.; Brocato, Rebecca L.
- Frontiers in Microbiology, Vol. 8
Blurred vision and myopic shift in Puumala virus infections are independent of disease severity
journal, October 2012
- Theiler, G.; Langer-Wegscheider, B.; Zollner-Schwetz, I.
- Clinical Microbiology and Infection, Vol. 18, Issue 10
Hantaviruses: A Global Disease Problem
journal, June 1997
- Schmaljohn, Connie
- Emerging Infectious Diseases, Vol. 3, Issue 2
Hypophyseal Hemorrhage and Panhypopituitarism during Puumala Virus Infection: Magnetic Resonance Imaging and Detection of Viral Antigen in the Hypophysis
journal, July 2002
- Hautala, Timo; Sironen, Tarja; Vapalahti, Olli
- Clinical Infectious Diseases, Vol. 35, Issue 1
Biphasic Emetic Response of Cyclophosphamide in the Ferret
journal, September 1997
- Wong, Richard H.; Lao, Lixing; Berman, Brian M.
- Pharmacology Biochemistry and Behavior, Vol. 58, Issue 1
Clinical Characteristics of Nephropathia Epidemica in Sweden: Prospective Study of 74 Cases
journal, November 1989
- Settergren, B.; Juto, P.; Trollfors, B.
- Clinical Infectious Diseases, Vol. 11, Issue 6
Intranasal monkeypox marmoset model: Prophylactic antibody treatment provides benefit against severe monkeypox virus disease
journal, June 2018
- Mucker, Eric M.; Wollen-Roberts, Suzanne E.; Kimmel, Adrienne
- PLOS Neglected Tropical Diseases, Vol. 12, Issue 6
Situation of hantavirus infections and haemorrhagic fever with renal syndrome in European countries as of December 2006
journal, July 2008
- Heyman, P.; Vaheri, A.
- Eurosurveillance, Vol. 13, Issue 28
A small nonhuman primate model for filovirus-induced disease
journal, November 2011
- Carrion, Ricardo; Ro, Youngtae; Hoosien, Kareema
- Virology, Vol. 420, Issue 2
A Phase 1 clinical trial of Hantaan virus and Puumala virus M-segment DNA vaccines for haemorrhagic fever with renal syndrome delivered by intramuscular electroporation
journal, May 2014
- Hooper, J. W.; Moon, J. E.; Paolino, K. M.
- Clinical Microbiology and Infection, Vol. 20
A Macaque Model for Hantavirus Infection
journal, July 1995
- Groen, J.; Gerding, M.; Koeman, J. P.
- Journal of Infectious Diseases, Vol. 172, Issue 1
A Hantavirus Pulmonary Syndrome (HPS) DNA Vaccine Delivered Using a Spring-powered Jet Injector Elicits a Potent Neutralizing Antibody Response in Rabbits and Nonhuman Primates
journal, August 2014
- Kwilas, Steve; Kishimori, Jennifer; Josleyn, Matthew
- Current Gene Therapy, Vol. 14, Issue 3
Synthesis of 1-β-d-ribofuranosyl-3-ethynyl-[1,2,4]triazole and its in vitro and in vivo efficacy against Hantavirus
journal, July 2008
- Chung, Dong-Hoon; Kumarapperuma, Sidath C.; Sun, Yanjie
- Antiviral Research, Vol. 79, Issue 1
Ocular characteristics in Nephropathia epidemica or Puumala virus infection
journal, December 1996
- Kontkanen, Matti; Puustjärvi, Tuomo; Kauppi, Paula
- Acta Ophthalmologica Scandinavica, Vol. 74, Issue 6
A Novel Nonhuman Primate Model for Influenza Transmission
journal, November 2013
- Moncla, Louise H.; Ross, Ted M.; Dinis, Jorge M.
- PLoS ONE, Vol. 8, Issue 11
DNA Vaccination with Hantavirus M Segment Elicits Neutralizing Antibodies and Protects against Seoul Virus Infection
journal, March 1999
- Hooper, J. W.; Kamrud, K. I.; Elgh, F.
- Virology, Vol. 255, Issue 2
Hantavirus Infections in Europe
journal, October 2003
- Vapalahti, Olli; Mustonen, Jukka; Lundkvist, Åke
- The Lancet Infectious Diseases, Vol. 3, Issue 10
Efficacy of arbidol on lethal hantaan virus infections in suckling mice and in vitro
journal, June 2009
- Deng, Hai-ying; Luo, Fan; Shi, Li-qiao
- Acta Pharmacologica Sinica, Vol. 30, Issue 7
Observations on Natural and Laboratory Infection of Rodents with the Etiologic Agent of Korean Hemorrhagic Fever *
journal, March 1981
- French, G. R.; Tsuchiya, K.; Baek, L. J.
- The American Journal of Tropical Medicine and Hygiene, Vol. 30, Issue 2
Detection of Puumala Hantavirus Antigen in Human Intestine during Acute Hantavirus Infection
journal, May 2014
- Latus, Joerg; Tenner-Racz, Klara; Racz, Paul
- PLoS ONE, Vol. 9, Issue 5
Time to revise the paradigm of hantavirus syndromes? Hantavirus pulmonary syndrome caused by European hantavirus
journal, January 2011
- Rasmuson, J.; Andersson, C.; Norrman, E.
- European Journal of Clinical Microbiology & Infectious Diseases, Vol. 30, Issue 5
Nephropathia Epidemica in Finland: A Retrospective Study of 126 Cases
journal, January 1994
- Mustonen, Jukka; Brummer-Korvenkontio, Markus; Hedman, Klaus
- Scandinavian Journal of Infectious Diseases, Vol. 26, Issue 1
Hantaan Virus Surveillance Targeting Small Mammals at Nightmare Range, a High Elevation Military Training Area, Gyeonggi Province, Republic of Korea
journal, April 2015
- Klein, Terry A.; Kim, Heung-Chul; Chong, Sung-Tae
- PLOS ONE, Vol. 10, Issue 4
Quantification of Hantaan Virus with a SYBR Green Ⅰ-Based One-Step qRT-PCR Assay
journal, November 2013
- Jiang, Wei; Yu, Hai-tao; Zhao, Ke
- PLoS ONE, Vol. 8, Issue 11
Common marmoset (Callithrix jacchus) as a primate model of dengue virus infection: development of high levels of viraemia and demonstration of protective immunity
journal, June 2011
- Omatsu, T.; Moi, M. L.; Hirayama, T.
- Journal of General Virology, Vol. 92, Issue 10
A Novel Highly Reproducible and Lethal Nonhuman Primate Model for Orthopox Virus Infection
journal, April 2010
- Kramski, Marit; Mätz-Rensing, Kerstin; Stahl-Hennig, Christiane
- PLoS ONE, Vol. 5, Issue 4
DNA vaccine-derived human IgG produced in transchromosomal bovines protect in lethal models of hantavirus pulmonary syndrome
journal, November 2014
- Hooper, J. W.; Brocato, R. L.; Kwilas, S. A.
- Science Translational Medicine, Vol. 6, Issue 264
Pathology of Experimental SARS Coronavirus Infection in Cats and Ferrets
journal, July 2008
- van den Brand, J. M. A.; Haagmans, B. L.; Leijten, L.
- Veterinary Pathology, Vol. 45, Issue 4
Antigenic and genetic properties of viruses linked to hemorrhagic fever with renal syndrome
journal, March 1985
- Schmaljohn, C.; Hasty, S.; Dalrymple, J.
- Science, Vol. 227, Issue 4690
Case Report: Clinical Pathologic Changes in Two Marmosets with Wasting Syndrome
journal, November 1996
- Logan, Ava C.; Khan, Kanwar Nasir M.
- Toxicologic Pathology, Vol. 24, Issue 6
Common Marmosets (Callithrix jacchus) as a Nonhuman Primate Model To Assess the Virulence of Eastern Equine Encephalitis Virus Strains
journal, July 2008
- Adams, A. P.; Aronson, J. F.; Tardif, S. D.
- Journal of Virology, Vol. 82, Issue 18
The Protean Manifestations of Hemorrhagic Fever with Renal Syndrome: A Retrospective Review of 26 Cases from Korea
journal, September 1990
- Bruno, Philip
- Annals of Internal Medicine, Vol. 113, Issue 5
Characterization and outcome following Puumala virus infection: a retrospective analysis of 75 cases
journal, March 2010
- Braun, N.; Haap, M.; Overkamp, D.
- Nephrology Dialysis Transplantation, Vol. 25, Issue 9
A lethal disease model for New World hantaviruses using immunosuppressed Syrian hamsters
journal, October 2017
- Vergote, Valentijn; Laenen, Lies; Vanmechelen, Bert
- PLOS Neglected Tropical Diseases, Vol. 11, Issue 10
Puumala virus infection in Syrian hamsters (Mesocricetus auratus) resembling hantavirus infection in natural rodent hosts
journal, September 2011
- Sanada, Takahiro; Kariwa, Hiroaki; Nagata, Noriyo
- Virus Research, Vol. 160, Issue 1-2
A unifying hypothesis and a single name for a complex globally emerging infection: hantavirus disease
journal, November 2011
- Clement, J.; Maes, P.; Lagrou, K.
- European Journal of Clinical Microbiology & Infectious Diseases, Vol. 31, Issue 1
A Phase 1 clinical trial of Hantaan virus and Puumala virus M-segment DNA vaccines for hemorrhagic fever with renal syndrome
journal, March 2012
- Boudreau, Ellen F.; Josleyn, Matthew; Ullman, Diane
- Vaccine, Vol. 30, Issue 11
The SARS-CoV ferret model in an infection–challenge study
journal, April 2008
- Chu, Yong-Kyu; Ali, Georgia D.; Jia, Fuli
- Virology, Vol. 374, Issue 1
A Neutralizing Human Monoclonal Antibody Protects against Lethal Disease in a New Ferret Model of Acute Nipah Virus Infection
journal, October 2009
- Bossart, Katharine N.; Zhu, Zhongyu; Middleton, Deborah
- PLoS Pathogens, Vol. 5, Issue 10
Morbillivirus Control of the Interferon Response: Relevance of STAT2 and mda5 but Not STAT1 for Canine Distemper Virus Virulence in Ferrets
journal, December 2013
- Svitek, N.; Gerhauser, I.; Goncalves, C.
- Journal of Virology, Vol. 88, Issue 5
The pathogenesis of nephropathia epidemica: New knowledge and unanswered questions
journal, December 2013
- Mustonen, Jukka; Mäkelä, Satu; Outinen, Tuula
- Antiviral Research, Vol. 100, Issue 3
Prolonged survival of Puumala hantavirus outside the host: evidence for indirect transmission via the environment
journal, August 2006
- Kallio, E. R.
- Journal of General Virology, Vol. 87, Issue 8
The ferret as a model organism to study influenza A virus infection
journal, August 2011
- Belser, J. A.; Katz, J. M.; Tumpey, T. M.
- Disease Models & Mechanisms, Vol. 4, Issue 5
Central nervous system-related symptoms and findings are common in acute Puumala hantavirus infection
journal, May 2010
- Hautala, Timo; Mähönen, Saara-Mari; Sironen, Tarja
- Annals of Medicine, Vol. 42, Issue 5
Ribavirin Therapy for Hantaan Virus Infection in Suckling Mice
journal, March 1986
- Huggins, J. W.; Kim, G. R.; Brand, O. M.
- Journal of Infectious Diseases, Vol. 153, Issue 3
Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease
journal, July 2015
- Mucker, Eric M.; Chapman, Jennifer; Huzella, Louis M.
- PLOS ONE, Vol. 10, Issue 7
Reference intervals for some clinical chemical parameters in the marmoset ( Callithrix jacchus ): effect of age and sex
journal, April 1984
- Davy, C. W.; Jackson, M. R.; Walker, J.
- Laboratory Animals, Vol. 18, Issue 2
A Lethal Disease Model for Hantavirus Pulmonary Syndrome
journal, October 2001
- Hooper, J. W.; Larsen, T.; Custer, D. M.
- Virology, Vol. 289, Issue 1
Ecology of Hantaan virus at Twin Bridges Training Area, Gyeonggi Province, Republic of Korea, 2005-2007
journal, November 2009
- Sames, William J.; Klein, Terry A.; Kim, Heung Chul
- Journal of Vector Ecology, Vol. 34, Issue 2
Appearance of renal hemorrhage in adult mice after inoculation of patient-derived hantavirus
journal, January 2017
- Shimizu, Kenta; Koma, Takaaki; Yoshimatsu, Kumiko
- Virology Journal, Vol. 14, Issue 1
Haematological and serum chemistry profiles of ferrets ( Mustela putorius furo )
journal, April 1982
- Lee, Elsbeth J.; Moore, W. E.; Fryer, H. C.
- Laboratory Animals, Vol. 16, Issue 2
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