RESUMO
Andes virus and Choclo virus are agents of hantavirus pulmonary syndrome. Andes virus in hamsters almost always causes a disease that is pathologically indistinguishable from fatal hantavirus pulmonary syndrome. The purpose of this study was to assess the pathogenicity of Choclo virus in hamsters. None of 18 hamsters infected with Choclo virus exhibited any symptom of disease. No evidence of inflammation or edema was found in the lungs of the 10 animals killed on days 7, 9, 11, 13, and 16 post-inoculation or in the lungs of the 8 animals killed on day 28 post-inoculation; however, hantavirus antigen was present in large numbers of endothelial cells in the microvasculature of the lungs of the animals killed on days 7, 9, 11, and 13 post-inoculation. These results suggest that infection in the microvasculature of lung tissue alone does not result in the life-threatening pulmonary edema in hamsters infected with Andes virus.
Assuntos
Infecções por Hantavirus/veterinária , Orthohantavírus/isolamento & purificação , Animais , Animais de Laboratório , Bunyaviridae/isolamento & purificação , Cricetinae , Feminino , Febre , Orthohantavírus/classificação , Mesocricetus , Doenças dos Roedores/virologia , Índice de Gravidade de Doença , TexasRESUMO
UNLABELLED: BACKGROUND. Ribavirin is active in vitro against hantaviruses, but the findings of an open trial of the use of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome (HCPS) were inconclusive. METHODS: Subjects with suspected HCPS in the prodrome or cardiopulmonary phase but without shock were eligible for randomization to receive either intravenous ribavirin (33 mg/kg [Assuntos
Antivirais/administração & dosagem
, Antivirais/uso terapêutico
, Síndrome Pulmonar por Hantavirus/tratamento farmacológico
, Ribavirina/administração & dosagem
, Ribavirina/uso terapêutico
, Adulto
, Antivirais/efeitos adversos
, Método Duplo-Cego
, Feminino
, Síndrome Pulmonar por Hantavirus/mortalidade
, Humanos
, Injeções Intravenosas
, Masculino
, Pessoa de Meia-Idade
, América do Norte/epidemiologia
, Placebos
, Ribavirina/efeitos adversos
RESUMO
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.