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1.
Free Radic Biol Med ; 42(12): 1826-37, 2007 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-17512462

RESUMO

It is unknown whether nutritional deficiencies affect the morphology and function of structural cells, such as epithelial cells, and modify the susceptibility to viral infections. We developed an in vitro system of differentiated human bronchial epithelial cells (BEC) grown either under selenium-adequate (Se+) or selenium-deficient (Se-) conditions, to determine whether selenium deficiency impairs host defense responses at the level of the epithelium. Se- BECs had normal SOD activity, but decreased activity of the selenium-dependent enzyme GPX1. Interestingly, catalase activity was also decreased in Se- BECs. Both Se- and Se+ BECs differentiated into a mucociliary epithelium; however, Se- BEC demonstrated increased mucus production and increased Muc5AC mRNA levels. This effect was also seen in Se+ BEC treated with 3-aminotriazole, an inhibitor of catalase activity, suggesting an association between catalase activity and mucus production. Both Se- and Se+ were infected with influenza A/Bangkok/1/79 and examined 24 h postinfection. Influenza-induced IL-6 production was greater while influenza-induced IP-10 production was lower in Se- BECs. In addition, influenza-induced apoptosis was greater in Se- BEC as compared to the Se+ BECs. These data demonstrate that selenium deficiency has a significant impact on the morphology and influenza-induced host defense responses in human airway epithelial cells.


Assuntos
Brônquios/efeitos dos fármacos , Vírus da Influenza A/efeitos dos fármacos , Influenza Humana/imunologia , Selênio/deficiência , Adulto , Alantoína/metabolismo , Animais , Brônquios/citologia , Brônquios/metabolismo , Catalase/antagonistas & inibidores , Catalase/efeitos dos fármacos , Catalase/metabolismo , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/metabolismo , Células Cultivadas/ultraestrutura , Quimiocina CXCL10 , Quimiocinas CXC/metabolismo , Galinhas , Cães , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Glutationa/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Humanos , Vírus da Influenza A/imunologia , Vírus da Influenza A/patogenicidade , Influenza Humana/metabolismo , Interleucina-6/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Selênio/administração & dosagem , Taxa de Sobrevida , Virulência/efeitos dos fármacos
2.
J Am Coll Nutr ; 20(5 Suppl): 384S-388S; discussion 396S-397S, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11603647

RESUMO

Malnutrition has long been associated with increased susceptibility to infectious disease. The increase in severity from and susceptibility to infectious disease in malnourished hosts is thought to be the result of an impaired immune response. For example, malnutrition could influence the immune response by inducing a less effective ability to manage the challenge of an infectious disease. Work in our laboratory has demonstrated that not only is the host affected by the nutritional deficiency, but the invading pathogen is as well. Using a deficiency in selenium (Se) as a model system, mice deficient in Se were more susceptible to infection with coxsackievirus, as well as with influenza virus. Se-deficient mice develop myocarditis when infected with a normally benign strain of coxsackievirus. They also develop severe pneumonitis when infected with a mild strain of influenza virus. The immune system was altered in the Se-deficient animals, as was the viral pathogen itself. Sequencing of viral isolates recovered from Se-deficient mice demonstrated mutations in the viral genome of both coxsackievirus and influenza virus. These changes in the viral genome are associated with the increased pathogenesis of the virus. The antioxidant selenoenzyme, glutathione peroxidase-1, was found to be critically important, as glutathione peroxidase knockout mice developed myocarditis, similar to the Se-deficient mice, when infected with the benign strain of myocarditis. This work points to the importance of host nutrition in not only optimizing the host immune response, but also in preventing viral mutations which could increase the viral pathogenicity.


Assuntos
Antioxidantes/metabolismo , Distúrbios Nutricionais/complicações , Selênio/deficiência , Viroses/imunologia , Viroses/virologia , Animais , Infecções por Coxsackievirus/imunologia , Suscetibilidade a Doenças , Enterovirus/genética , Enterovirus/imunologia , Enterovirus/patogenicidade , Genoma Viral , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Humanos , Camundongos , Camundongos Knockout , Mutação , Miocardite/imunologia , Miocardite/virologia , Orthomyxoviridae/genética , Orthomyxoviridae/imunologia , Orthomyxoviridae/patogenicidade , Virulência
5.
J Infect Dis ; 182 Suppl 1: S93-6, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10944489

RESUMO

The nutritional status of the host has long been associated with both severity and susceptibility to infectious disease. The accepted model system proposes that inadequate nutrition impairs the functioning of the immune system, thus resulting in increased susceptibility to infection. However, current work suggests that not only can the nutritional status of the host affect the immune response, but it can also affect the viral pathogen. In a mouse model, a benign strain of coxsackievirus B3 became virulent and caused myocarditis in selenium- and vitamin E-deficient mice. This change in pathogenicity was due to mutations in the viral genome, which changed an avirulent virus into a virulent one. Once these mutations occurred, even mice with normal nutriture developed disease from the mutated virus. These results suggest that the oxidative stress status of the host can have a profound influence on a viral pathogen.


Assuntos
Estado Nutricional , Viroses/fisiopatologia , Animais , Cardiomiopatias/epidemiologia , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , China/epidemiologia , Cuba/epidemiologia , Humanos , Camundongos , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Estresse Oxidativo , Vírus de RNA/genética , Vírus de RNA/fisiologia , Selênio/deficiência
6.
Am J Clin Nutr ; 71(6 Suppl): 1676S-81S, 2000 06.
Artigo em Inglês | MEDLINE | ID: mdl-10837315

RESUMO

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 , Ratos
7.
Proc Nutr Soc ; 59(4): 581-5, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11115793

RESUMO

Previous work in our laboratory demonstrated that a virus could undergo rapid mutation in a host deficient in Se, leading to a normally avirulent virus acquiring virulence due to genome changes. Once these mutations occur, even a host with adequate Se-nutriture is susceptible to the newly virulent virus. What influence does the deficiency in Se have on the immune response of the host? Infection with myocarditic strains of coxsackievirus induces an inflammatory response in the cardiac tissue. It is this immune response that induces the heart damage, rather than direct viral effects on the heart tissue. Chemokines are chemo-attractant molecules that are secreted during an infection in order to attract immune cells to the site of the injury, and have been found to be important for the development of coxsackievirus-induced myocarditis. We found that a deficiency in Se influences the expression of mRNA for the chemokine monocyte chemo-attractant protein-1, which may have implications for the development of myocarditis in the Se-deficient host. Expression of mRNA for interferon-gamma was also greatly decreased in the Se-deficient animal. Thus, a deficiency in Se can have profound effects on the host as well as on the virus itself. How the alteration of the immune response of the Se-deficient animal affects the development of the virulent genotype remains to be answered.


Assuntos
Quimiocinas/genética , Infecções por Coxsackievirus/imunologia , Enterovirus Humano B/imunologia , Micronutrientes/deficiência , Miocardite/imunologia , Selênio/deficiência , Animais , Quimiocinas/imunologia , Infecções por Coxsackievirus/virologia , Enterovirus Humano B/patogenicidade , Genótipo , Interferon gama , Camundongos , Micronutrientes/imunologia , Mutação , Miocardite/virologia , RNA Mensageiro , Selênio/imunologia , Virulência
8.
Proc Nutr Soc ; 58(3): 707-11, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10604206

RESUMO

The association between viral disease and nutrition has long been thought to be due to effects on the host immune system. This theory suggests that when a host is malnourished, the immune system is compromised, and thus increased susceptibility to viral infection will occur. However, the virus itself may also be affected by the nutritional status of the host. We have demonstrated that a normally-benign strain of coxsackievirus B3 (CVB3/0) becomes virulent in either Se-deficient or vitamin E-deficient mice. Although the deficient animals are immunosuppressed, the virus itself is also altered. Six nucleotide changes were found in the virus that replicated in the deficient mice, and once these mutations occurred, even mice with normal nutrition became susceptible to disease. Thus, the nutritional status of the host was able to transform an avirulent virus into a virulent one due to genomic changes in the virus. We believe that a common mechanism of oxidative stress is the underlying cause of the genetic changes. Both vitamin E and Se act as antioxidants, and benign virus inoculated into GSH peroxidase (EC 1.11.1.9)-knockout mice will also convert to virulence due to genomic changes. Our work points to the importance of host nutrition during a viral disease, not only from the perspective of the host, but from the perspective of the viral pathogen as well.


Assuntos
Imunidade Inata , Selênio/fisiologia , Viroses/imunologia , Animais , Cardiomiopatias/virologia , Infecções por Coxsackievirus/imunologia , Enterovirus Humano B/genética , Glutationa Peroxidase/genética , Humanos , Camundongos , Camundongos Knockout , Doenças do Sistema Nervoso/virologia , Estresse Oxidativo , Selênio/deficiência
9.
Phytochemistry ; 50(2): 329-32, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9933948

RESUMO

The aqueous EtOH extract of aerial parts of Eschscholtzia californica Cham. yielded six flavonol 3-O-glycosides including two new compounds: quercetin 3-O-[alpha-rhamnopyranosyl-(1-4)-alpha-rhamnopyranosyl-(1-6)-beta- glucopyranoside] and isorhamnetin 3-O-[alpha-rhamnopyranosyl-(1-4)-alpha-rhamnopyranosyl-(1-6)-beta- glucopyranoside]. Their structures were established on the basis of spectroscopic studies.


Assuntos
Flavonoides/química , Glicosídeos/isolamento & purificação , Papaver/química , Plantas Medicinais , Flavonóis , Glicosídeos/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas/métodos , Estrutura Molecular , Espectrofotometria Ultravioleta
10.
Br Med Bull ; 55(3): 528-33, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10746343

RESUMO

A mouse model of coxsackievirus-induced myocarditis is being used to investigate nutritional determinants of viral virulence. This approach was suggested by research carried out in China which showed that mice fed diets composed of low selenium ingredients from a Keshan disease area suffered more extensive heart damage when infected with a coxsackie B4 virus than infected mice fed the same diet but supplemented with selenium by esophageal intubation. Selenium deficiency in our mice increased the virulence of an already virulent strain of coxsackievirus B3 (CVB3/20) and also allowed conversion of a non-virulent strain (CVB3/0) to virulence. Such conversion of CVB3/0 was accompanied by a change in the viral genome to more closely match that of the virulent virus, CVB3/20. As far as the authors are aware, this is the first report of host nutrition influencing the genetic make-up of an invading pathogen. Nutritionists may need to consider this mechanism of increased viral virulence in order to gain a better understanding of diet/infection relationships.


Assuntos
Enterovirus Humano B/patogenicidade , Genoma Viral , Miocardite/virologia , Selênio/deficiência , Animais , Enterovirus Humano B/efeitos dos fármacos , Enterovirus Humano B/genética , Camundongos , Virulência , Deficiência de Vitamina E/virologia
11.
Planta Med ; 65(3): 296, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17260311
12.
Annu Rev Nutr ; 18: 93-116, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9706220

RESUMO

Oxidative stress is implicated in the pathogenesis of several viral infections, including hepatitis, influenza, and AIDS. Dietary oxidative stress due to either selenium or vitamin E deficiency increases cardiac damage in mice infected with a myocarditic strain of coxsackievirus B3. Such dietary oxidative stress also allows a normally benign (i.e., amyocarditic) coxsackievirus B3 to convert to virulence and cause heart damage. This conversion to virulence is due to a nucleotide sequence change in the genome of the benign virus, which then resembles more closely the nucleotide sequence of virulent strains. Although it has been known for many years that poor nutrition can affect host response to infection, this is the first report of host nutrition affecting the genetic sequence of a pathogen. Further research is needed to determine whether poor host nutrition plays any role in the emergence of new viral diseases via alterations in he genotype of an infectious agent.


Assuntos
Dieta , Estresse Oxidativo , Viroses , Animais , Humanos , Fenômenos Fisiológicos da Nutrição , Selênio/deficiência , Deficiência de Vitamina E
14.
Biomed Environ Sci ; 10(2-3): 307-15, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9315324

RESUMO

Keshan disease, an endemic cardiomyopathy in China, can be prevented with selenium (Se) supplementation. However, the seasonal and annual nature of the disease suggests that an infectious co-factor is required along with a deficiency in Se. Using a murine model of coxsackievirus B3 (CVB3)-induced myocarditis, Se-deficient mice were shown to be more susceptible to the cardiopathologic effects of the virus. In addition, a normal benign strain of CVB3 becomes virulent in Se-deficient mice. This change in virulence was shown to be due to point mutations in the viral genome. Although the mechanism of the viral mutation is not known, the oxidative stress status of the Se-deficient host may play a role, either by directly affecting the virus and/or affecting host immune defenses.


Assuntos
Evolução Biológica , Deficiências Nutricionais/virologia , Enterovirus Humano B/genética , Selênio/deficiência , Animais , Infecções por Coxsackievirus/complicações , Infecções por Coxsackievirus/imunologia , Deficiências Nutricionais/complicações , Deficiências Nutricionais/imunologia , Modelos Animais de Doenças , Enterovirus Humano B/patogenicidade , Genoma Viral , Camundongos , Miocardite/complicações , Miocardite/virologia , Mutação Puntual
15.
J Nutr ; 127(5 Suppl): 966S-970S, 1997 05.
Artigo em Inglês | MEDLINE | ID: mdl-9164275

RESUMO

Nutrition has long been known to affect the ability of the host to respond to infectious disease. Widespread famines are often accompanied by increased morbidity and mortality due to infectious diseases. The currently accepted view of the relationship between nutrition of the host and its susceptibility to infectious disease is one of a direct relationship with host immune status. That is, if the nutritional status of the host is poor-due to either single or multiple nutrient deficiencies-then the functioning of the host immune system is compromised. This impairment of the immune response will lead to an increased susceptibility to infectious disease. Clearly, the immune response has been shown to be weakened by inadequate nutrition in many model systems and in human studies. However, what about the effect of host nutrition on the pathogen itself? Our laboratory has shown, using a mouse model of coxsackievirus-induced myocarditis, that a host deficiency in either selenium or vitamin E leads to a change in viral phenotype, such that an avirulent strain of the virus becomes virulent and a virulent strain becomes more virulent. The change in phenotype was shown to be due to point mutations in the viral genome. Once the mutations occur, the phenotype change is stable and can now be expressed even in mice of normal nutriture. Our results suggest that nutrition can affect not only the host, but the pathogen as well, and demonstrate a new model of relating host nutritional effects to viral pathogenesis.


Assuntos
Infecções por Coxsackievirus , Enterovirus Humano B/patogenicidade , Selênio/deficiência , Deficiência de Vitamina E/virologia , Animais , Infecções por Coxsackievirus/imunologia , Infecções por Coxsackievirus/patologia , Infecções por Coxsackievirus/virologia , Modelos Animais de Doenças , Enterovirus Humano B/genética , Coração/virologia , Camundongos , Camundongos Endogâmicos C3H , Miocárdio/patologia
16.
Planta Med ; 63(1): 63-5, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17252330

RESUMO

A simultaneous separation of the enantiomers of kawain, dihydrokawain, methysticin, and dihydromethysticin as well as the achiral dienolides yangonin and demethoxyyangonin was carried out on a ChiraSpher NT column. This HPLC method can be used for the investigation of the enantiomeric purity of plant material and herbal medicines. The influence of temperature and flow rate are discussed in respect to the chromatographic resolution of the enantiomers. All tested enolide racemates can be preparatively separated on ChiraSpher NT.

17.
Biol Trace Elem Res ; 56(1): 5-21, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9152508

RESUMO

In 1979, Chinese scientists reported that selenium had been linked to Keshan disease, an endemic juvenile cardiomyopathy found in China. However, certain epidemiological features of the disease could not be explained solely on the basis of inadequate selenium nutrition. Fluctuations in the seasonal incidence of the disease suggested involvement of an infectious agent. Indeed, a coxsackievirus B4 isolated from a Keshan disease victim caused more heart muscle damage when inoculated into selenium-deficient mice than when given to selenium-adequate mice. Those results led us to study the relationship of nutritional status to viral virulence. Coxsackievirus B3/0 (CVB3/0), did not cause disease when inoculated into mice fed adequate levels of Se and vitamin E. However, mice fed diets deficient in either Se or vitamin E developed heart lesions when infected with CVB3/0. To determine if the change in viral phenotype was maintained, we passaged virus isolated from Se-deficient hosts, designated as CVB3/0 Se-, back into Se-adequate hosts. The CVB3/0 Se- virus caused disease in Se-adequate mice. To determine if the phenotype change was due to changes in the viral genome, we sequenced viruses isolated from Se-deficient mice and compared them with the input CVB3/0 virus. Six point mutations differed between the parent strain and the recovered CVB3/0 Se- isolates. When the experiment was repeated using vitamin E-deficient mice, the same 6 point mutations were found. This is the first report of a specific host nutritional deficiency altering viral genotype. Keshan disease may be the result of several interacting causes including a dominant nutritional deficiency (selenium), other nutritional factors (vitamin E, polyunsaturated fatty acids), and an infectious agent (virus).


Assuntos
Cardiomiopatias/etiologia , Enterovirus Humano B/patogenicidade , Selênio/deficiência , Deficiência de Vitamina E/complicações , Animais , Modelos Animais de Doenças , Enterovirus Humano B/genética , Humanos , Camundongos , Miocardite/etiologia , Estado Nutricional , Estresse Oxidativo , Virulência
19.
Nat Med ; 1(5): 433-6, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7585090

RESUMO

Previous work from our laboratory demonstrated that selenium deficiency in the mouse allows a normally benign (amyocarditic) cloned and sequenced Coxackievirus to cause significant heart damage. Furthermore, Coxsackievirus recovered from the hearts of selenium-deficient mice inoculated into selenium-adequate mice still induced significant heart damage, suggesting that the amyocarditic Coxsackievirus had mutated to a virulent phenotype. Here we report that sequence analysis revealed six nucleotide changes between the virulent virus recovered from the selenium-deficient host and the avirulent input virus. These nucleotide changes are consistent with known differences in base composition between virulent and avirulent strains of Coxsackievirus. To the best of our knowledge, this is the first report of a specific nutritional deficiency driving changes in a viral genome, permitting an avirulent virus to acquire virulence due to genetic mutation.


Assuntos
Infecções por Coxsackievirus/etiologia , Enterovirus Humano B/genética , Miocardite/etiologia , Selênio/deficiência , Animais , Evolução Biológica , Infecções por Coxsackievirus/genética , DNA Viral/análise , Enterovirus Humano B/patogenicidade , Coração/virologia , Camundongos , Camundongos Endogâmicos C3H , Mutação/genética , Miocardite/genética , Análise de Sequência de DNA , Virulência
20.
J Infect Dis ; 170(2): 351-7, 1994 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8035022

RESUMO

Coxsackievirus B3 (CVB3/20)-induced myocarditic lesions occurred more quickly and were more severe and virus titers in heart and liver were higher in selenium (Se)-deficient than Se-adequate mice. NK cell activity and serum neutralizing antibody titers were similar in both Se-adequate and -deficient CVB3/20-infected mice; however, lymphocyte proliferation to both mitogen and antigen was decreased in Se-deficient mice. CVB3/20 isolated from Se-deficient donor mice and inoculated into Se-adequate recipient mice induced severe myocarditis. In contrast, CVB3/20 isolated from Se-adequate donor mice and inoculated into Se-adequate recipient mice induced only moderate myocarditis, similar to that caused by the original virus stock. Thus, the general population of CVB3/20 virions, as a consequence of replicating in an Se-deficient host, underwent a phenotypic change to increased virulence. These results have important implications for the emergence of virulent viruses.


Assuntos
Infecções por Coxsackievirus/microbiologia , Enterovirus Humano B/patogenicidade , Miocardite/microbiologia , Selênio/deficiência , Animais , Infecções por Coxsackievirus/patologia , Glutationa Peroxidase/sangue , Coração/microbiologia , Células Matadoras Naturais/imunologia , Fígado/microbiologia , Ativação Linfocitária , Masculino , Camundongos , Miocardite/patologia , Miocárdio/patologia , Inoculações Seriadas , Virulência
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