RESUMO
The discovery that the juvenile cardiomyopathy known as Keshan disease likely has a dual etiology that involves both a nutritional deficiency of the essential trace mineral selenium (Se) as well as an infection with an enterovirus provided the impetus for additional studies of relationships between nutrition and viral infection. An amyocarditic strain of coxsackievirus B3, CVB3/0, converted to virulence when it was inoculated into Se-deficient mice. This conversion was accompanied by changes in the genetic structure of the virus so that its genome closely resembled that of other known virulent CVB3 strains. Similar alterations in virulence and genomic composition of CVB3/0 could be observed in mice fed normal diets but genetically deprived of the antioxidant selenoenzyme glutathione peroxidase (knockout mice). More recent research has shown that a mild strain of influenza virus, influenza A/Bangkok/1/79, also exhibits increased virulence when given to Se-deficient mice. This increased virulence is accompanied by multiple changes in the viral genome in a segment previously thought to be relatively stable. Epidemic neuropathy in Cuba has features that suggest a combined nutritional/viral etiology. Further research, both basic and applied, is needed to assess properly the possible role of malnutrition in contributing to the emergence of novel viral diseases.
Assuntos
Genoma Viral , Selênio/deficiência , Oligoelementos/deficiência , Viroses/etiologia , Animais , Infecções por Coxsackievirus/etiologia , Cuba/epidemiologia , Enterovirus/genética , Infecções por Enterovirus/etiologia , Humanos , Doenças do Sistema Nervoso/epidemiologia , Orthomyxoviridae/genética , Viroses/epidemiologiaAssuntos
Infecções por Coxsackievirus/diagnóstico , Infecções por Coxsackievirus/epidemiologia , Infecções por Coxsackievirus/etiologia , Infecções por Coxsackievirus/imunologia , Infecções por Coxsackievirus/patologia , Infecções por Coxsackievirus/prevenção & controle , Infecções por Coxsackievirus/terapiaRESUMO
It has long been known that the nutritional status of the host can influence both susceptibility to infectious disease and the severity of the disease if contracted. In studies of coxsackievirus infection and selenium deficiency in mice, we found that mice fed a selenium-deficient diet developed myocarditis, but mice fed a diet adequate in selenium did not. Similarly, mice fed a diet deficient in vitamin E developed myocarditis, but mice fed a diet with adequate vitamin E did not. The epidemic of optic and peripheral neuropathy that occurred in Cuba in the early 1990s provides another example of how the nutritional status of the host may affect the impact of a virus. Patients who developed neuropathy had lower blood concentrations of riboflavin, vitamin E, selenium, alpha- and beta-carotenes, and the carotenoid lycopene, which suggests that the disease was associated with an impairment of protective antioxidant pathways. After supplementation of the population with these nutrients, the disease began to subside. The nutritional status of the host can have a profound influence on a virus, so that a normally avirulent virus becomes virulent because of changes in the viral genome. Our studies suggest that outbreaks of disease attributed to a nutritional deficiency may actually result from infection by a virus that has become pathogenic by replicating in a nutritionally deficient host.
Assuntos
Infecções por Coxsackievirus/etiologia , Estresse Oxidativo , Doenças do Sistema Nervoso Periférico/epidemiologia , Selênio/deficiência , Deficiência de Vitamina E/complicações , Animais , Infecções por Coxsackievirus/enzimologia , Cuba/epidemiologia , Surtos de Doenças , Glutationa Peroxidase/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Humanos , Camundongos , Camundongos Knockout , Miocardite/etiologia , Estado Nutricional , Doenças do Sistema Nervoso Periférico/etiologia , Fenótipo , RatosRESUMO
OBJECTIVE: To investigate the possibility of a viral agent in the central nervous system of patients with epidemic neuropathy. DESIGN: Virus isolation attempts, in cell cultures and suckling mice, from cerebrospinal fluid (CSF) of neuropathy patients and controls undergoing lumbar puncture for unrelated reasons. Serologic studies in patients, contacts, and controls. SETTING: An epidemic of optic and peripheral neuropathy affected more than 50,000 people in Cuba in 1991 through 1993. Illness was associated with dietary limitations and increased physical demands accompanying the shortages of food and fuel experienced in Cuba since 1989. Most patients responded to parenteral vitamin therapy, and the epidemic began to subside when oral vitamin supplementation was begun for the entire Cuban population. RESULTS: Coxsackievirus A9 (five isolates) and a similar, less cytopathic virus (100 isolates) were recovered from 105 (84%) of 125 CSF specimens from neuropathy patients. The strains with light cytopathic effect were antigenically related to Coxsackieviruses A9 and B4 by cross-neutralization and immunoblotting assays. Virus persisted in CSF of some patients for 1 to 12 months. Cerebrospinal fluid from patients and both types of virus from cell culture produced illness, including complete posterior flaccid paralysis, in newborn mice, and virus was reisolated from the mice. Mouse tissues and sural nerve biopsy specimens from patients were stained by immunoperoxidase and colloidal gold techniques using hyperimmune rabbit antisera against the virus with light cytopathic effect. CONCLUSIONS: Coxsackievirus A9 or an antigenically related agent with a light cytopathic effect was present in CSF of 84% of 125 patients with epidemic neuropathy. The role of these agents, probably in combination with nutritional factors, in the pathophysiology of the disease requires further investigation.
Assuntos
Infecções por Coxsackievirus/etiologia , Surtos de Doenças , Enterovirus/isolamento & purificação , Neurite Óptica/virologia , Doenças do Sistema Nervoso Periférico/virologia , Adulto , Animais , Animais Lactentes/virologia , Anticorpos Antivirais/análise , Antígenos Virais/análise , Técnicas de Cultura de Células , Líquido Cefalorraquidiano/virologia , Chlorocebus aethiops , Infecções por Coxsackievirus/líquido cefalorraquidiano , Infecções por Coxsackievirus/epidemiologia , Infecções por Coxsackievirus/patologia , Cuba/epidemiologia , Efeito Citopatogênico Viral , Enterovirus/imunologia , Enterovirus/patogenicidade , Feminino , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Neurite Óptica/líquido cefalorraquidiano , Neurite Óptica/epidemiologia , Neurite Óptica/patologia , Sistema Nervoso Periférico/patologia , Sistema Nervoso Periférico/virologia , Doenças do Sistema Nervoso Periférico/líquido cefalorraquidiano , Doenças do Sistema Nervoso Periférico/epidemiologia , Doenças do Sistema Nervoso Periférico/patologia , Coelhos , Células Vero/virologiaRESUMO
Aborda as infecçöes por coxsackievirus, sua etiologia, imunidade, epidemiologia, patogenia, patologia, manifestaçöes clínicas, diagnóstico e tratamento. (MC)
Assuntos
Infecções por Coxsackievirus , Infecções por Coxsackievirus/diagnóstico , Infecções por Coxsackievirus/epidemiologia , Infecções por Coxsackievirus/etiologiaRESUMO
In order to characterize viral kinetics and pathogenic properties of two intratypic variants of coxsackievirus B type 3, Balb/c mice were intraperitoneally inoculated and serial samples harvested from days 2 to 28. Although both CB3o (amyocarditic) and CB3m (myocarditic) variants induced similar early infectivity titres in pancreas, only the latter led to severe acinar necrosis, followed in turn by patent viraemia and subsequent focal myocarditis. Nevertheless, when both variants were inoculated in cultured cardiac cells, neither infectivity nor cell death rate differed noticeable. Therefore, our findings indicate that overt myocarditis is not attributable to contrasting cardiomyocyte susceptibility to the tested variants but rather to prior viral events in pancreatic tissues.
Assuntos
Infecções por Coxsackievirus/etiologia , Enterovirus Humano B/patogenicidade , Miocardite/etiologia , Pancreatite/etiologia , Animais , Células Cultivadas , Infecções por Coxsackievirus/microbiologia , Infecções por Coxsackievirus/patologia , Enterovirus Humano B/genética , Enterovirus Humano B/fisiologia , Variação Genética , Camundongos , Camundongos Endogâmicos BALB C , Miocardite/microbiologia , Miocardite/patologia , Especificidade de Órgãos , Pancreatite/microbiologia , Pancreatite/patologia , Viremia/etiologia , Replicação ViralRESUMO
No clinical, cytochemical nor electroencephalographic standards of behavior, specific for each etiology were found in a series of 67 cases of viral infection of the nervous system; however, the severeness was greater in cases of infectious mononucleosis with encephalic involvement and in cases caused by Coxsackie B5 possibly because these appeared in younger patients. The group with greater percentage of definitive motor and intellectual sequelae was found in cases with infectious mononucleosis and ECHO. Cases due to herpes simplex were not more severe during the acute stage, but followed a course with an important percentage of definitive sequelae. Meningoencephalitides from parotiditis were milder, and only in one case did they show permanent motor sequelae.