Role of mixed Th1 and Th2 serum cytokines on pathogenesis and prognosis of hantavirus pulmonary syndrome

Borges, Alessandra Abel; Campos, Geraldo Maia; Moreli, Marcos Lázaro; Souza, Rodrigo Wagner Alves de; Saggioro, Fabiano Pinto; Figueiredo, Glauciane Garcia de; Livonesi, Márcia Cristina; Figueiredo, Luíz Tadeu Moraes

doi:10.1016/j.micinf.2008.06.006

Cited by 55 publications

(67 citation statements)

References 27 publications

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“…Patients infected with hantaviruses have elevated levels of proinflammatory cytokines and frequencies of virus-specific CD8 ϩ T cells but decreased regulatory T (Treg) cell activity and Treg cell numbers (14,35,44,47,49,81). Concentrations of the regulatory cytokine transforming growth factor ␤1 (TGF-␤1) are also reduced in HCPS patients (9) and in Syrian hamster models of HCPS (65).…”

mentioning

confidence: 99%

Seoul Virus-Infected Rat Lung Endothelial Cells and Alveolar Macrophages Differ in Their Ability To Support Virus Replication and Induce Regulatory T Cell Phenotypes

Klein

2012

J Virol

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confidence: 99%

Seoul Virus-Infected Rat Lung Endothelial Cells and Alveolar Macrophages Differ in Their Ability To Support Virus Replication and Induce Regulatory T Cell Phenotypes

Klein

2012

J Virol

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“…This hypothesis is based largely on analysis of a limited number of clinical samples from confirmed symptomatic cases and cell culture models (9,(30)(31)(32)(33). A limitation in addressing this hypothesis process experimentally has been a lack of appropriate animal models for hantaviral disease.…”

Section: Discussionmentioning

confidence: 99%

Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques

Safronetz¹,

Prescott²,

Feldmann³

et al. 2014

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

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The pathophysiology of hantavirus pulmonary syndrome (HPS) remains unclear because of a lack of surrogate disease models with which to perform pathogenesis studies. Nonhuman primates (NHP) are considered the gold standard model for studying the underlying immune activation/suppression associated with immunopathogenic viruses such as hantaviruses; however, to date an NHP model for HPS has not been described. Here we show that rhesus macaques infected with Sin Nombre virus (SNV), the primary etiological agent of HPS in North America, propagated in deer mice develop HPS, which is characterized by thrombocytopenia, leukocytosis, and rapid onset of respiratory distress caused by severe interstitial pneumonia. Despite establishing a systemic infection, SNV differentially activated host responses exclusively in the pulmonary endothelium, potentially the mechanism leading to acute severe respiratory distress. This study presents a unique chronological characterization of SNV infection and provides mechanistic data into the pathophysiology of HPS in a closely related surrogate animal model. We anticipate this model will advance our understanding of HPS pathogenesis and will greatly facilitate research toward the development of effective therapeutics and vaccines against hantaviral diseases.

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“…In contrast, human disease is characterized by a vascular leak syndrome and thrombocytopenia without signs of virus-induced damage to the endothelium (11,(14)(15)(16)(17)(18), the principal target of infection in both humans and rodents (2,18). Inflammatory virus-specific T cells have been isolated from, and inflammatory cytokines detected in, hantavirus patients and autopsy specimens (19)(20)(21); thus, it has been speculated that the immune response contributes to pathogenesis.…”

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confidence: 99%

Differential Lymphocyte and Antibody Responses in Deer Mice Infected with Sin Nombre Hantavirus or Andes Hantavirus

Schountz

Quackenbush

Rovnak

et al. 2014

J Virol

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Hantavirus cardiopulmonary syndrome (HCPS) is a rodent-borne disease with a high case-fatality rate that is caused by several New World hantaviruses. Each pathogenic hantavirus is naturally hosted by a principal rodent species without conspicuous disease and infection is persistent, perhaps for life. Deer mice (Peromyscus maniculatus) are the natural reservoirs of Sin Nombre virus (SNV), the etiologic agent of most HCPS cases in North America. Deer mice remain infected despite a helper T cell response that leads to high-titer neutralizing antibodies. Deer mice are also susceptible to Andes hantavirus (ANDV), which causes most HCPS cases in South America; however, deer mice clear ANDV. We infected deer mice with SNV or ANDV to identify differences in host responses that might account for this differential outcome. SNV RNA levels were higher in the lungs but not different in the heart, spleen, or kidneys. Most ANDV-infected deer mice had seroconverted 14 days after inoculation, but none of the SNV-infected deer mice had. Examination of lymph node cell antigen recall responses identified elevated immune gene expression in deer mice infected with ANDV and suggested maturation toward a Th2 or T follicular helper phenotype in some ANDV-infected deer mice, including activation of the interleukin 4 (IL-4) pathway in T cells and B cells. These data suggest that the rate of maturation of the immune response is substantially higher and of greater magnitude during ANDV infection, and these differences may account for clearance of ANDV and persistence of SNV. IMPORTANCEHantaviruses persistently infect their reservoir rodent hosts without pathology. It is unknown how these viruses evade sterilizing immune responses in the reservoirs. We have determined that infection of the deer mouse with its homologous hantavirus, Sin Nombre virus, results in low levels of immune gene expression in antigen-stimulated lymph node cells and a poor antibody response. However, infection of deer mice with a heterologous hantavirus, Andes virus, results in a robust lymph node cell response, signatures of T and B cell maturation, and production of antibodies. These findings suggest that an early and aggressive immune response to hantaviruses may lead to clearance in a reservoir host and suggest that a modest immune response may be a component of hantavirus ecology.

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Role of mixed Th1 and Th2 serum cytokines on pathogenesis and prognosis of hantavirus pulmonary syndrome

Cited by 55 publications

References 27 publications

Seoul Virus-Infected Rat Lung Endothelial Cells and Alveolar Macrophages Differ in Their Ability To Support Virus Replication and Induce Regulatory T Cell Phenotypes

Seoul Virus-Infected Rat Lung Endothelial Cells and Alveolar Macrophages Differ in Their Ability To Support Virus Replication and Induce Regulatory T Cell Phenotypes

Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques

Differential Lymphocyte and Antibody Responses in Deer Mice Infected with Sin Nombre Hantavirus or Andes Hantavirus

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