Maporal Viral Infection in the Syrian Golden Hamster: A Model of Hantavirus Pulmonary Syndrome

Milazzo, Mary Louise; Eyzaguirre, Eduardo; Molina, Claudia P.; Fulhorst, Charles F.

doi:10.1086/344735

Cited by 82 publications

(83 citation statements)

References 6 publications

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“…In contrast, levels of antigen appear to be higher in Syrian golden hamsters infected with the human-pathogenic Andes, Maporal (MAPV), or Choclo (CHOV) hantaviruses (11,18,25), although only ANDV and MAPV are pathogenic in hamsters. SNV causes an apathogenic infection in hamsters and elicits a strong neutralizing antibody response by 28 dpi (18); thus, it may be informative to examine the kinetics of neutralizing antibodies in this model.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of Immune Responses in Deer Mice Experimentally Infected with Sin Nombre Virus

Schountz

Acuña-Retamar

Feinstein

et al. 2012

J Virol

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Deer mice are the principal reservoir hosts of Sin Nombre virus, the etiologic agent of most hantavirus cardiopulmonary syndrome cases in North America. Infection of deer mice results in persistence without conspicuous pathology, and most, if not all, infected mice remain infected for life, with periods of viral shedding. The kinetics of viral load, histopathology, virus distribution, and immune gene expression in deer mice were examined. Viral antigen was detected as early as 5 days postinfection and peaked on day 15 in the lungs, hearts, kidneys, and livers. Viral RNA levels varied substantially but peaked on day 15 in the lungs and heart, and antinucleocapsid IgG antibodies appeared in some animals on day 10, but a strong neutralizing antibody response failed to develop during the 20-day experiment. No clinical signs of disease were observed in any of the infected deer mice. Most genes were repressed on day 2, suggesting a typical early downregulation of gene expression often observed in viral infections. Several chemokine and cytokine genes were elevated, and markers of a T cell response occurred but then declined days later. Splenic transforming growth factor beta (TGF-β) expression was elevated early in infection, declined, and then was elevated again late in infection. Together, these data suggest that a subtle immune response that fails to clear the virus occurs in deer mice.

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Section: Discussionmentioning

confidence: 99%

Kinetics of Immune Responses in Deer Mice Experimentally Infected with Sin Nombre Virus

Schountz

Acuña-Retamar

Feinstein

et al. 2012

J Virol

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“…The dichotomy of immune responses between humans and rodent reservoirs also suggests that TGF-␤ 1 may be a potential therapeutic agent for treating immunopathologies caused by hantaviruses, which could abrogate the fatal inflammation associated with HCPS. Hamster models of HCPS are available that have similar pathogenesis to human HCPS (61)(62)(63) and could be used to test this hypothesis. The use of corticosteroid antiinflammatory approaches to hantavirus disease has had recent success (64); however, further work will be required to determine whether antiinflammatory cytokine therapies can be used safely and effectively without causing persistent infection.…”

Section: Discussionmentioning

confidence: 99%

Regulatory T cell-like responses in deer mice persistently infected with Sin Nombre virus

Schountz

Prescott²,

Cogswell³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

107

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Hantavirus cardiopulmonary syndrome is a zoonotic illness associated with a systemic inflammatory immune response, capillary leak, noncardiogenic pulmonary edema, and shock in humans. Cytokines, including TNF, IFN-␥, and lymphotoxin, are thought to contribute to its pathogenesis. In contrast, infected rodent reservoirs of hantaviruses experience few or no pathologic changes and the host rodent can remain persistently infected for life. Generally, it is unknown why such dichotomous immune responses occur between humans and reservoir hosts. Thus, we examined CD4 ؉ T cell responses from one such reservoir, the deer mouse (Peromy-

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“…However, SNV does not cause disease in infected mice. Some strains of New World hantaviruses, although not SNV, have been shown to cause disease in Syrian golden hamsters (34,35), but few immunologic reagents exist for studying hamsters. Thus, it is necessary to study HPS in patients infected with SNV.…”

Section: Virus-specific Cd8mentioning

confidence: 99%

Role of Specific CD8+ T Cells in the Severity of a Fulminant Zoonotic Viral Hemorrhagic Fever, Hantavirus Pulmonary Syndrome

Kilpatrick¹,

Terajima²,

Koster

et al. 2004

The Journal of Immunology

154

174

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We report on the role of specific CD8+ T cells in the pathogenesis of a highly lethal human viral disease, hantavirus pulmonary syndrome (HPS). HPS is a zoonotic disease caused by transmission of Sin Nombre virus (SNV) from chronically infected deer mice. In humans, this fulminant infection is characterized by lung capillary leakage, respiratory failure, and cardiogenic shock. Individuals with HLA-B*3501 have an increased risk of developing severe HPS, suggesting that CD8+ T cell responses to SNV contribute to pathogenesis. We identified three CD8+ T cell epitopes in SNV presented by HLA-B*3501 and quantitated circulating SNV-specific CD8+ T cells in 11 acute HPS patients using HLA/peptide tetramers. We found significantly higher frequencies of SNV-specific T cells in patients with severe HPS requiring mechanical ventilation (up to 44.2% of CD8+ T cells) than in moderately ill HPS patients hospitalized but not requiring mechanical ventilation (up to 9.8% of CD8+ T cells). These results imply that virus-specific CD8+ T cells contribute to HPS disease outcome. Intense CD8+ T cell responses to SNV may be induced by the encounter of the unnatural human host to this zoonotic virus without coevolution. This may also be the immunopathologic basis of other life-threatening human virus infections.

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Maporal Viral Infection in the Syrian Golden Hamster: A Model of Hantavirus Pulmonary Syndrome

Cited by 82 publications

References 6 publications

Kinetics of Immune Responses in Deer Mice Experimentally Infected with Sin Nombre Virus

Kinetics of Immune Responses in Deer Mice Experimentally Infected with Sin Nombre Virus

Regulatory T cell-like responses in deer mice persistently infected with Sin Nombre virus

Role of Specific CD8+ T Cells in the Severity of a Fulminant Zoonotic Viral Hemorrhagic Fever, Hantavirus Pulmonary Syndrome

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