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1.
Nat Commun ; 11(1): 1522, 2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-32251280

RESUMO

Foxp3+ regulatory T (Treg) cells are essential for maintaining peripheral tolerance and preventing autoimmunity. While genetic factors may predispose for autoimmunity, additional environmental triggers, such as viral infections, are usually required to initiate the onset of disease. Here, we show that viral infection with LCMV results in type I IFN-dependent Treg cell loss that is rapidly compensated by the conversion and expansion of Vß5+ conventional T cells into iTreg cells. Using Vß5-deficient mice, we show that these Vß5+ iTreg cells are dispensable for limiting anti-viral immunity. Rather, the delayed replenishment of Treg cells in Vß5-deficient mice compromises suppression of microbiota-dependent activation of CD8+ T cells, resulting in colitis. Importantly, recovery from clinical symptoms in IBD patients is marked by expansion of the corresponding Vß2+ Treg population in humans. Collectively, we provide a link between a viral trigger and an impaired Treg cell compartment resulting in the initiation of immune pathology.


Assuntos
Infecções por Arenaviridae/imunologia , Autoimunidade , Linfócitos T CD8-Positivos/imunologia , Colite/imunologia , Vírus da Coriomeningite Linfocítica/imunologia , Linfócitos T Reguladores/imunologia , Animais , Infecções por Arenaviridae/complicações , Linhagem Celular , Colite/microbiologia , Colo/imunologia , Colo/microbiologia , Fatores de Transcrição Forkhead/metabolismo , Microbioma Gastrointestinal/imunologia , Voluntários Saudáveis , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Ativação Linfocitária/genética , Masculino , Camundongos , Camundongos Knockout , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Linfócitos T Reguladores/metabolismo
2.
J Exp Clin Cancer Res ; 39(1): 34, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041643

RESUMO

Odontogenic tumors (OT) are considered rare events and their epidemiologic data are scarce and under-estimated in developing countries because there is no systematic collection of clinical features including histological analyses of the tissue samples. Furthermore, there is an underestimation of the disease relevance and affected people are often marginalized in spite of severe functional impairment of aero-digestive tract. Etiology of OT in humans is still unknown and it represents an important therapeutic and diagnostic challenge.Lassa fever is an acute viral haemorrhagic illness caused by Lassa virus, a member of the arenavirus family of viruses. The disease is endemic in the rodent population in West-East Africa. Humans usually become infected with Lassa virus through exposure to the food or household items contaminated with urine or feces of infected rats. It is also reported person-to-person infections. About 80% of people infected by Lassa virus have no symptoms but the virus establishes a life-long persistent infection.The present commentary significance is to start, for the first time ever, a systematic collection of clinical features and tissue sample collection at the St. Mary's Hospital in Lacor (Gulu) North Uganda where the considered pathologies have an important frequency. The systematic collection will allow to corroborate the possible association between arenaviruses infection and pathogenesis of odontogenic tumors in humans.


Assuntos
Infecções por Arenaviridae/complicações , Infecções por Arenaviridae/virologia , Arenavirus/fisiologia , Transformação Celular Viral , Tumores Odontogênicos/etiologia , Infecções por Arenaviridae/epidemiologia , Biópsia , Suscetibilidade a Doenças , Humanos , Febre Lassa/complicações , Febre Lassa/virologia , Vírus Lassa , Tumores Odontogênicos/diagnóstico , Tumores Odontogênicos/epidemiologia , Uganda
3.
Clin Immunol ; 205: 75-82, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31175964

RESUMO

Considerable evidence indicates that autoimmune disease expression depends on both genetic and environmental factors. Among potential environmental triggers, occupational airway exposure to crystalline silica and virus infections have been linked to lupus and other autoimmune diseases in both humans and mouse models. Here, we hypothesized that combined silica and virus exposures synergize and induce autoimmune manifestations more effectively than single exposure to either of these factors, particularly in individuals with low genetic predisposition. Accordingly, infection with the model murine pathogen lymphocytic choriomenigitis virus (LCMV) in early life, followed by airway exposure to crystalline silica in adult life, induced lupus-like autoantibodies to several nuclear self-antigens including chromatin, RNP and Sm, concurrent with kidney lesions, in non-autoimmune C57BL/6 (B6) mice. In contrast, given individually, LCMV or silica were largely ineffectual in this strain. These results support a multihit model of autoimmunity, where exposure to different environmental factors acting on distinct immunostimulatory pathways complements limited genetic predisposition and increases the risk of autoimmunity above a critical threshold.


Assuntos
Infecções por Arenaviridae/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Rim/imunologia , Pulmão/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Vírus da Coriomeningite Linfocítica , Dióxido de Silício/toxicidade , Silicose/imunologia , Animais , Infecções por Arenaviridae/complicações , Doenças Autoimunes/etiologia , Doenças Autoimunes/patologia , Cromatina/imunologia , Doença Crônica , Interação Gene-Ambiente , Predisposição Genética para Doença , Rim/patologia , Pulmão/patologia , Lúpus Eritematoso Sistêmico/patologia , Camundongos , Camundongos Endogâmicos C57BL , Ribonucleoproteínas/imunologia , Silicose/etiologia , Silicose/patologia
4.
Annu Rev Virol ; 4(1): 141-158, 2017 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-28645238

RESUMO

Hemorrhagic fevers caused by viruses were identified in the late 1950s in South America. These viruses have existed in their hosts, the New World rodents, for millions of years. Their emergence as infectious agents in humans coincided with changes in the environment and farming practices that caused explosions in their host rodent populations. Zoonosis into humans likely occurs because the pathogenic New World arenaviruses use human transferrin receptor 1 to enter cells. The mortality rate after infection with these viruses is high, but the mechanism by which disease is induced is still not clear. Possibilities include direct effects of cellular infection or the induction of high levels of cytokines by infected sentinel cells of the immune system, leading to endothelia and thrombocyte dysfunction and neurological disease. Here we provide a review of the ecology and molecular and cellular biology of New World arenaviruses, as well as a discussion of the current animal models of infection. The development of animal models, coupled with an improved understanding of the infection pathway and host response, should lead to the discovery of new drugs for treating infections.


Assuntos
Infecções por Arenaviridae/virologia , Arenavirus do Novo Mundo/genética , Arenavirus do Novo Mundo/patogenicidade , Animais , Antígenos CD/metabolismo , Infecções por Arenaviridae/complicações , Infecções por Arenaviridae/imunologia , Infecções por Arenaviridae/transmissão , Arenavirus do Novo Mundo/imunologia , Modelos Animais de Doenças , Febres Hemorrágicas Virais/transmissão , Febres Hemorrágicas Virais/virologia , Interações Hospedeiro-Patógeno , Humanos , Camundongos , Receptores da Transferrina/metabolismo , Receptores Virais/metabolismo , Roedores/virologia , Zoonoses/virologia
6.
Biomédica (Bogotá) ; 33(supl.1): 99-107, set. 2013. tab
Artigo em Espanhol | LILACS | ID: lil-695801

RESUMO

Introducción. La región de Urabá es endémica para varias enfermedades febriles agudas de origen infeccioso. Sin embargo, solo los pacientes con malaria pueden acceder a un diagnóstico oportuno y rápido, motivo por el cual muchos síndromes febriles no palúdicos quedan sin diagnóstico etiológico claro. Objetivo. Establecer la etiología, describir las manifestaciones clínicas y explorar algunos posibles factores de riesgo relacionados con los síndromes febriles agudos no palúdicos en pacientes procedentes de los municipios de Necoclí, Turbo y Apartadó. Materiales y métodos. Se tomaron muestras de suero en fase aguda y de convalecencia de 220 pacientes febriles negativos para malaria, provenientes de zonas rurales y urbanas de Necoclí, Turbo y Apartadó en los años 2007 y 2008. Se practicaron pruebas para diagnóstico de dengue (detección de anticuerpos IgM por ELISA), leptospirosis (detección de anticuerpos IgM e IgG por IFI), rickettsiosis (detección de anticuerpos IgG por IFI), hantavirus y arenavirus (detección de anticuerpos IgG por ELISA). Resultados. Se encontraron frecuencias de dengue, leptospirosis, rickettsiosis y arenavirus de 37,3 %, 14,1 %, 2,7 % y 0,5 %, respectivamente. Se presentaron 12 casos de coinfección de leptospirosis-dengue y uno de leptospirosis-rickettsiosis-dengue. El sexo masculino y la humedad relativa media, fueron factores de riesgo para dengue. El inicio de signos clínicos en febrero de 2008, se asoció tanto con la infección por dengue como por leptospirosis. Conclusión. Se reafirma la importancia del virus del dengue, Rickettsia spp. y Leptospira spp., como agentes causantes del síndrome febril en la región del Urabá.


Introduction: Urabá, a region on the northern coast of Colombia, is endemic to several acute febrile illnesses of infectious origin; however, only patients with malaria may have access to quick and effective diagnosis. For this reason, many non-malarial febrile patients go without a clear etiologic diagnosis. Aim: To establish the etiology and clinical signs of acute febrile non-malaria syndromes and explore some of the likely risk factors in patients originating in the municipalities of Necocli, Turbo and Apartado who exhibit these symptoms. Materials and methods: We obtained acute and convalescent sera from 220 non-malarial febrile patients from the rural and urban zones of Necocli, Turbo and Apartado during 2007 and 2008. Serologic tests for dengue (IgM by ELISA), leptospirosis (IgM and IgG by IFA), rickettsiosis (IgG by IFI), hanta and arenavirus (IgG by ELISA) were performed. Results: We found that the frequency of infection for dengue, leptospirosis, rickettsiosis and arenavirus, was 37.3%; 14.1%; 2.7% and 0.5%, respectively. There were 12 co-infection cases of leptospirosis-dengue and one of leptospirosis-rickettsiosis-dengue. Male gender and relative humidity were considered risk factors for dengue, and the beginning of clinical signs in February of 2008 was associated with the infection of dengue and leptospirosis. Conclusion: This study confirms previous records that underline the importance of Rickettsia spp, dengue virus and Leptospira spp as causal agents of febrile syndrome in this region of Colombia.


Assuntos
Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Arenaviridae/epidemiologia , Dengue/epidemiologia , Febre de Causa Desconhecida/etiologia , Leptospirose/epidemiologia , Infecções por Rickettsia/epidemiologia , Doença Aguda , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Infecções por Arenaviridae/sangue , Infecções por Arenaviridae/complicações , Colômbia , Convalescença , Dengue/sangue , Dengue/complicações , Infecções por Hantavirus/complicações , Infecções por Hantavirus/epidemiologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Leptospirose/sangue , Leptospirose/complicações , Prevalência , Estudos Retrospectivos , População Rural , Infecções por Rickettsia/sangue , Infecções por Rickettsia/complicações , Estudos Soroepidemiológicos , Avaliação de Sintomas , População Urbana
7.
Biomedica ; 33 Suppl 1: 99-107, 2013 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-24652254

RESUMO

INTRODUCTION: Urabá, a region on the northern coast of Colombia, is endemic to several acute febrile illnesses of infectious origin; however, only patients with malaria may have access to quick and effective diagnosis. For this reason, many non-malarial febrile patients go without a clear etiologic diagnosis. AIM: To establish the etiology and clinical signs of acute febrile non-malaria syndromes and explore some of the likely risk factors in patients originating in the municipalities of Necocli, Turbo and Apartado who exhibit these symptoms. MATERIALS AND METHODS: We obtained acute and convalescent sera from 220 non-malarial febrile patients from the rural and urban zones of Necocli, Turbo and Apartado during 2007 and 2008. Serologic tests for dengue (IgM by ELISA), leptospirosis (IgM and IgG by IFA), rickettsiosis (IgG by IFI), hanta and arenavirus (IgG by ELISA) were performed. RESULTS: We found that the frequency of infection for dengue, leptospirosis, rickettsiosis and arenavirus, was 37.3%; 14.1%; 2.7% and 0.5%, respectively. There were 12 co-infection cases of leptospirosis-dengue and one of leptospirosis-rickettsiosis-dengue. Male gender and relative humidity were considered risk factors for dengue, and the beginning of clinical signs in February of 2008 was associated with the infection of dengue and leptospirosis. CONCLUSION: This study confirms previous records that underline the importance of Rickettsia spp, dengue virus and Leptospira spp as causal agents of febrile syndrome in this region of Colombia.


Assuntos
Infecções por Arenaviridae/epidemiologia , Dengue/epidemiologia , Febre de Causa Desconhecida/etiologia , Leptospirose/epidemiologia , Infecções por Rickettsia/epidemiologia , Doença Aguda , Adolescente , Adulto , Idoso , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Infecções por Arenaviridae/sangue , Infecções por Arenaviridae/complicações , Criança , Pré-Escolar , Colômbia , Convalescença , Dengue/sangue , Dengue/complicações , Feminino , Infecções por Hantavirus/complicações , Infecções por Hantavirus/epidemiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Leptospirose/sangue , Leptospirose/complicações , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Infecções por Rickettsia/sangue , Infecções por Rickettsia/complicações , População Rural , Estudos Soroepidemiológicos , Avaliação de Sintomas , População Urbana
8.
Am J Transplant ; 9(11): 2479-84, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19843029

RESUMO

Viral infections including those due to cytomegalovirus have been associated with accelerated cardiac allograft vasculopathy (CAV) in clinical trials and some animal models. Evidence demonstrating a direct causal relationship between such infections and de novo formation of coronary vascular lesions is lacking. Heterotopic murine cardiac transplants were performed in a parental to F1 combination in animals lacking both T- and B-lymphocytes (RAG(-/-)). Coronary vasculopathy developed almost exclusively in the presence of recipient infection with lymphocytic choriomeningitis virus but not in uninfected controls. This process was also dependent upon the presence of natural killer (NK) cells as depletion of NK cells abrogated the process. These data show that a viral infection in its native host, and not previously implicated in the production of CAV, can contribute to the development of advanced coronary vascular lesions in cardiac allotransplants in mice. These data also suggest that virus-induced CAV can develop via an NK-cell-dependent pathway in the absence of T- and B-lymphocytes.


Assuntos
Infecções por Arenaviridae/imunologia , Doença das Coronárias/virologia , Transplante de Coração , Hospedeiro Imunocomprometido , Células Matadoras Naturais/virologia , Vírus da Coriomeningite Linfocítica , Animais , Infecções por Arenaviridae/complicações , Linfócitos B/imunologia , Doença das Coronárias/imunologia , Sobrevivência de Enxerto/imunologia , Proteínas de Homeodomínio/genética , Células Matadoras Naturais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Linfócitos T/imunologia , Imunologia de Transplantes , Transplante Homólogo
10.
PLoS One ; 3(11): e3725, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19008960

RESUMO

A growing number of arenaviruses are known to cause viral hemorrhagic fever (HF), a severe and life-threatening syndrome characterized by fever, malaise, and increased vascular permeability. Ribavirin, the only licensed antiviral indicated for the treatment of certain arenaviral HFs, has had mixed success and significant toxicity. Since severe arenaviral infections initially do not present with distinguishing symptoms and are difficult to clinically diagnose at early stages, it is of utmost importance to identify antiviral therapies effective at later stages of infection. We have previously reported that T-705, a substituted pyrazine derivative currently under development as an anti-influenza drug, is highly active in hamsters infected with Pichinde virus when the drug is administered orally early during the course of infection. Here we demonstrate that T-705 offers significant protection against this lethal arenaviral infection in hamsters when treatment is begun after the animals are ill and the day before the animals begin to succumb to disease. Importantly, this coincides with the time when peak viral loads are present in most organs and considerable tissue damage is evident. We also show that T-705 is as effective as, and less toxic than, ribavirin, as infected T-705-treated hamsters on average maintain their weight better and recover more rapidly than animals treated with ribavirin. Further, there was no added benefit to combination therapy with T-705 and ribavirin. Finally, pharmacokinetic data indicate that plasma T-705 levels following oral administration are markedly reduced during the latter stages of disease, and may contribute to the reduced efficacy seen when treatment is withheld until day 7 of infection. Our findings support further pre-clinical development of T-705 for the treatment of severe arenaviral infections.


Assuntos
Amidas/toxicidade , Amidas/uso terapêutico , Infecções por Arenaviridae/tratamento farmacológico , Febres Hemorrágicas Virais/tratamento farmacológico , Pirazinas/toxicidade , Pirazinas/uso terapêutico , Ribavirina/uso terapêutico , Absorção/efeitos dos fármacos , Administração Oral , Alanina Transaminase/sangue , Amidas/administração & dosagem , Amidas/sangue , Animais , Infecções por Arenaviridae/complicações , Infecções por Arenaviridae/patologia , Infecções por Arenaviridae/virologia , Aspartato Aminotransferases/sangue , Cricetinae , Modelos Animais de Doenças , Progressão da Doença , Feminino , Febres Hemorrágicas Virais/complicações , Febres Hemorrágicas Virais/patologia , Febres Hemorrágicas Virais/virologia , Interferon Tipo I/sangue , Hepatopatias/complicações , Hepatopatias/patologia , Hepatopatias/virologia , Mesocricetus , Vírus Pichinde/efeitos dos fármacos , Pirazinas/administração & dosagem , Pirazinas/sangue , Ribavirina/administração & dosagem , Análise de Sobrevida , Resultado do Tratamento , Carga Viral
11.
J Virol ; 81(18): 10101-12, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17626099

RESUMO

CCR5 and CXCR3 are important molecules in regulating the migration of activated lymphocytes. Thus, the majority of tissue-infiltrating T cells found in the context of autoimmune conditions and viral infections express CCR5 and CXCR3, and the principal chemokine ligands are expressed within inflamed tissues. Accordingly, intervention studies have pointed to nonredundant roles of these receptors in models of allograft rejection, viral infection, and autoimmunity. In spite of this, considerable controversy exists, with many studies failing to support a role for CCR5 or CXCR3 in disease pathogenesis. One possible explanation is that different chemokine receptors may take over in the absence of any individual receptor, thus rendering individual receptors redundant. We have attempted to address this issue by analyzing CCR5(-/-), CXCR3(-/-), and CCR5/CXCR3(-/-) mice with regard to virus-induced liver inflammation, generation and recruitment of effector cells, virus control, and immunopathology. Our results indicate that CCR5 and CXCR3 are largely dispensable for tissue infiltration and virus control. In contrast, the T-cell response is accelerated in CCR5(-/-) and CCR5/CXCR3(-/-) mice and the absence of CCR5 is associated with the induction of CD8(+) T-cell-mediated immunopathology consisting of marked hepatic microvesicular steatosis.


Assuntos
Infecções por Arenaviridae/imunologia , Movimento Celular/imunologia , Fígado Gorduroso/imunologia , Vírus da Coriomeningite Linfocítica/imunologia , Receptores CCR5/imunologia , Receptores de Quimiocinas/imunologia , Animais , Infecções por Arenaviridae/complicações , Infecções por Arenaviridae/genética , Infecções por Arenaviridae/patologia , Autoimunidade/genética , Linfócitos T CD8-Positivos , Movimento Celular/genética , Quimiocinas/imunologia , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Fígado Gorduroso/virologia , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Inflamação/virologia , Camundongos , Camundongos Knockout , Receptores CCR5/deficiência , Receptores CXCR3 , Receptores de Quimiocinas/deficiência
12.
Exp Biol Med (Maywood) ; 230(11): 865-71, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16339752

RESUMO

The Docile strain of lymphocytic choriomeningitis virus (LCMV) induces anemia in a number of inbred strains of mice, including C3HeB/FeJ and CBA/Ht animals. A difference in the kinetics of anemia and in compensatory reticulocytosis suggested that impaired erythropoiesis was the major pathogenic mechanism involved in CBA/Ht mice, but not in C3HeB/FeJ mice. In both mouse strains an antierythrocyte autoantibody production that depended on the presence of functional CD4+ T lymphocytes was observed. Although depletion of T helper lymphocytes prevented anemia in C3HeB/FeJ mice, this treatment largely failed to inhibit the development of the disease in CBA/Ht animals. This observation indicated that the antierythrocyte autoimmune response induced by the infection was at least partly responsible for the anemia of C3HeB/FeJ mice, but not of CBA/Ht mice. Erythrophagocytosis was enhanced in both mouse strains after LCMV infection, but did not appear to be a major cause of anemia. These data clearly indicate that similar disease profiles induced by the same virus in two different host strains can be the result of distinctly different mechanisms.


Assuntos
Anemia Hemolítica Autoimune/imunologia , Infecções por Arenaviridae/imunologia , Hematopoese/imunologia , Vírus da Coriomeningite Linfocítica , Anemia Hemolítica Autoimune/etiologia , Anemia Hemolítica Autoimune/patologia , Animais , Formação de Anticorpos/imunologia , Infecções por Arenaviridae/complicações , Infecções por Arenaviridae/patologia , Autoanticorpos/imunologia , Autofagia/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Eritrócitos/imunologia , Depleção Linfocítica , Vírus da Coriomeningite Linfocítica/imunologia , Camundongos , Camundongos Endogâmicos , Reticulocitose/imunologia , Especificidade da Espécie
13.
J Immunol ; 175(10): 6275-85, 2005 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-16272278

RESUMO

Human coinfection with the helminth parasite Schistosoma mansoni and hepatitis B and hepatitis C viruses is associated with increased hepatic viral burdens and severe liver pathology. In this study we developed a murine S. mansoni/lymphocytic choriomeningitis virus (LCMV) coinfection model that reproduces the enhanced viral replication and liver pathology observed in human coinfections, and used this model to explore the mechanisms involved. Viral coinfection during the Th2-dominated granulomatous phase of the schistosome infection resulted in induction of a strong LCMV-specific T cell response, with infiltration of high numbers of LCMV-specific IFN-gamma-producing CD8+ cells into the liver. This was associated with suppression of production of the Th2 cytokines dominant during S. mansoni infection and a rapid increase in morbidity, linked to hepatotoxicity. Interestingly, the liver of coinfected mice was extremely susceptible to viral replication. This correlated with a reduced intrahepatic type I IFN response following virus infection. Schistosome egg Ags were found to suppress the type I IFN response induced in murine bone marrow-derived dendritic cells by polyinosinic-polycytidylic acid. These results suggest that suppression of the antiviral type I IFN response by schistosome egg Ags in vivo predisposes the liver to enhanced viral replication with ensuing immunopathological consequences, findings that may be paralleled in human schistosome/hepatotropic virus coinfections.


Assuntos
Infecções por Arenaviridae/complicações , Infecções por Arenaviridae/imunologia , Hepatite Viral Animal/complicações , Hepatite Viral Animal/imunologia , Vírus da Coriomeningite Linfocítica , Esquistossomose mansoni/complicações , Esquistossomose mansoni/imunologia , Animais , Antígenos de Helmintos , Infecções por Arenaviridae/patologia , Infecções por Arenaviridae/virologia , Citocinas/biossíntese , Modelos Animais de Doenças , Hepatite Viral Animal/patologia , Hepatite Viral Animal/virologia , Humanos , Interferon Tipo I/biossíntese , Fígado/parasitologia , Fígado/patologia , Fígado/virologia , Vírus da Coriomeningite Linfocítica/patogenicidade , Vírus da Coriomeningite Linfocítica/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Contagem de Ovos de Parasitas , Schistosoma mansoni/imunologia , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/parasitologia , Células Th2/imunologia , Fatores de Tempo , Replicação Viral
14.
Math Biosci ; 186(2): 191-217, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14583172

RESUMO

An SI epidemic model for a host with two viral infections circulating within the population is developed, analyzed, and numerically simulated. The model is a system of four differential equations which includes a state for susceptible individuals, two states for individuals infected with a single virus, one which is vertically transmitted and the other which is horizontally transmitted, and a fourth state for individuals infected with both viruses. A general growth function with density-dependent mortality is assumed. A special case of this model, where there is no coinfection and total cross immunity, is thoroughly analyzed. Several threshold values are defined which determine establishment of the disease and persistence at equilibrium for one or both of the infections within the host population. The model has applications to a hantavirus and an arenavirus that infect cotton rats. The hantavirus is transmitted horizontally whereas the arenavirus is transmitted vertically. It is shown through analysis and numerical simulations that both diseases can be maintained within a single host population, where individuals can be either infected with both viruses or with a single virus.


Assuntos
Infecções por Hantavirus/transmissão , Modelos Biológicos , Orthohantavírus/patogenicidade , Animais , Infecções por Arenaviridae/complicações , Infecções por Arenaviridae/transmissão , Infecções por Hantavirus/complicações , Cinética , Dinâmica Populacional , Ratos
15.
Diabetes ; 52(8): 2025-34, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12882919

RESUMO

Pancreatic beta-cell antiviral defense plays a critical role in protection from coxsackievirus B4 (CVB4)-induced diabetes. In the present study, we tested the hypothesis that interferon (IFN)-induced antiviral defense determines beta-cell survival after infection by the human pathogen CVB3, cytomegalovirus (CMV), and lymphocytic choriomeningitis virus (LCMV). We demonstrated that mice harboring beta-cells that do not respond to IFN because of the expression of the suppressor of cytokine signaling-1 (SOCS-1) succumb to an acute form of type 1 diabetes after infection with CVB3. Interestingly, the tropism of the virus was altered in SOCS-1 transgenic (Tg) mice, and CVB3 was detected in islet cells of SOCS-1-Tg mice before beta-cell loss and the onset of diabetes. Furthermore, insulitis was increased in SOCS-1-Tg mice after infection with murine CMV, and a minority of the mice developed overt diabetes. However, infection with LCMV failed to cause beta-cell destruction in SOCS-1 Tg mice. These findings suggest that CVB3 can cause diabetes in a host lacking adequate beta-cell antiviral defense, and that incomplete target cell antiviral defense may enhance susceptibility to diabetes triggered by CMV. In conclusion, suppressed beta-cell antiviral defense reveals the diabetogenic potential of two pathogens previously linked to the onset of type 1 diabetes in humans.


Assuntos
Infecções por Citomegalovirus/complicações , Diabetes Mellitus Tipo 1/virologia , Peptídeos e Proteínas de Sinalização Intracelular , Ilhotas Pancreáticas/virologia , Proteínas Repressoras , Doença Aguda , Animais , Infecções por Arenaviridae/complicações , Infecções por Arenaviridae/imunologia , Proteínas de Transporte/genética , Infecções por Citomegalovirus/imunologia , Diabetes Mellitus Tipo 1/imunologia , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/imunologia , Humanos , Interferons/imunologia , Ilhotas Pancreáticas/imunologia , Vírus da Coriomeningite Linfocítica , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Camundongos Transgênicos , Muromegalovirus , Miocardite/virologia , Pancreatite/imunologia , Pancreatite/virologia , Proteína 1 Supressora da Sinalização de Citocina , Proteínas Supressoras da Sinalização de Citocina , Linfócitos T/imunologia
16.
Thromb Haemost ; 90(2): 326-33, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12888881

RESUMO

Hematologic involvement is the main feature of Argentine hemorrhagic fever (AHF), an endemo-epidemic disease caused by Junin virus (JV). Since endothelial dysfunction could play a role in AHF-altered hemostasis, we studied human umbilical vein endothelial cell (HUVEC) infection with a virulent (JVv) and a non-virulent (JVa) JV strain. Cells were infected by the two JV variants with no detectable apoptosis or cytopathic effect. Both viral variants up-regulated ICAM-1 and VCAM-1 levels, while von Willebrand factor (VWF) production was decreased. Prostacyclin (PGI2) release and decay accelerating factor (DAF) expression were greater in JVv- than in JVa-infected or control cells. Furthermore, nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) expression was only raised in JVv-infected supernatants. Significant NO and PGI2 values were also detected in AHF patient sera. These data demonstrate that endothelial cell responses are triggered subsequently by JV infection, suggesting that such alterations play a major role in the pathogenesis of AHF and perhaps in other viral-induced hemorrhagic diseases.


Assuntos
Infecções por Arenaviridae/complicações , Infecções por Arenaviridae/fisiopatologia , Endotélio Vascular/fisiopatologia , Febres Hemorrágicas Virais/fisiopatologia , Febres Hemorrágicas Virais/virologia , Vírus Junin , Apoptose , Infecções por Arenaviridae/sangue , Antígenos CD55/metabolismo , Células Cultivadas , Epoprostenol/metabolismo , Humanos , Óxido Nítrico/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de von Willebrand/metabolismo
17.
Nat Immunol ; 4(4): 343-9, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12627229

RESUMO

Polyclonal hypergammaglobulinemia is a characteristic of chronic inflammatory conditions, including persisting viral infections and autoimmune diseases. Here we have studied hypergammaglobulinemia in mice infected with lymphocytic choriomeningitis virus (LCMV), which induces nonspecific immunoglobulins as a result of switching natural IgM specificities to IgG. The process is dependent on help from CD4+ T cells that specifically recognize LCMV peptides presented by B cells on major histocompatibility complex class II molecules. Thus, hypergammaglobulinemia may arise when specific helper T cells recognize B cells that have processed viral antigens irrespective of the B cell receptor specificity. This nonspecific B cell activation may contribute to antibody-mediated autoimmunity.


Assuntos
Infecções por Arenaviridae/imunologia , Autoimunidade/imunologia , Hipergamaglobulinemia/imunologia , Vírus da Coriomeningite Linfocítica/imunologia , Animais , Antígenos Virais/imunologia , Infecções por Arenaviridae/complicações , Autoanticorpos/biossíntese , Autoanticorpos/imunologia , Linfócitos B/imunologia , Linfócitos B/virologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Citocinas/metabolismo , Hipergamaglobulinemia/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Superfície Celular/metabolismo , Carga Viral
18.
Am J Obstet Gynecol ; 187(6): 1715-6, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12501090

RESUMO

Lymphocytic choriomeningitis virus (LCMV), a rodent-borne arenavirus, is an often undiagnosed human fetal teratogen. We describe a neonate born with hydrocephalus and chorioretinitis after maternal second-trimester symptomatic LCMV infection. Previously reported affected infants are reviewed. We strongly suggest that obstetricians counsel their pregnant patients regarding the potential hazard that contact with infected pet, laboratory, and household mice and hamsters poses to pregnant women and their unborn children.


Assuntos
Infecções por Arenaviridae/congênito , Coriorretinite/virologia , Hidrocefalia/virologia , Vírus da Coriomeningite Linfocítica , Complicações Infecciosas na Gravidez/virologia , Animais , Infecções por Arenaviridae/complicações , Infecções por Arenaviridae/diagnóstico , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Camundongos , Gravidez , Zoonoses/virologia
19.
J Immunol ; 167(8): 4566-73, 2001 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-11591785

RESUMO

It has long been recognized that some viral infections result in generalized immune suppression. In acute infections, this period of suppressed immunity is relatively short. However, chronic infections associated with a prolonged period of immune suppression present far greater risks. Here, we examined the role of CD8 T cell responses following viral infection in immunity to systemic histoplasmosis. Although wild-type mice with systemic histoplasmosis were able to control the infection, those simultaneously infected with lymphocytic choriomeningitis virus clone 13 showed reduced immunity with greater fungal burden and high mortality. The immune suppression was associated with loss of CD4 T cells and B cells, generalized splenic atrophy, and inability to mount a granulomatous response. Removing the anti-viral CD8 T cells in the coinfected mice enabled them to reduce the fungal burden and survive the infection. Their lymphoid organs were replenished with CD4 T and B cells. In contrast to wild-type mice, perforin-deficient mice infected with lymphocytic choriomeningitis virus clone 13 and Histoplasma showed an absence of immunopathology, but the animals still died. These results show that CD8 T cells can suppress immunity through different mechanisms; although immunopathology is perforin-dependent, lethality is perforin-independent.


Assuntos
Infecções por Arenaviridae/imunologia , Linfócitos T CD8-Positivos/imunologia , Histoplasmose/imunologia , Vírus da Coriomeningite Linfocítica/imunologia , Animais , Infecções por Arenaviridae/complicações , Doença Crônica , Suscetibilidade a Doenças , Histoplasmose/complicações , Tolerância Imunológica , Depleção Linfocítica , Tecido Linfoide/imunologia , Glicoproteínas de Membrana/deficiência , Glicoproteínas de Membrana/imunologia , Camundongos , Perforina , Proteínas Citotóxicas Formadoras de Poros , Baço/patologia
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