Biomedical subjects

Melinda A Beck

Publications and source records attributed to Melinda A Beck.

9 recordsLinked to original sources

PubMed2006

An aged host promotes the evolution of avirulent coxsackievirus into a virulent strain.

The emergence of new, more pathogenic viruses necessitates elucidation of factors that promote viral evolution. Aging, a potential factor, is associated with increased susceptibility to viral infections. We used the enterovirus coxsackievirus B3 (CVB3) to investigate the effects of host age on pathogenicity and viral gene sequence. Old mice infected with a normally amyocarditic strain of CVB3, CVB3/0, had significantly higher mean heart viral titers compared with CVB3/0-infected adult mice. To determine whether a change in the CVB3/0 viral population could contribute to the higher titers observed in the old infected mice, CVB3/0 was passed once through an old or adult host and the changes in pathogenicity and viral genome were examined after subsequent infection of old or adult mice. Adult mice infected with CVB3/0 that was passed through an old host (CVB3/0(Old)) exhibited significantly higher heart viral titers, pathology, and weight loss than adult mice infected with either stock CVB3/0 or CVB3/0 passed through an adult host (CVB3/0(Adult)). Sequence analysis of virus isolated from CVB3/0(Old)-infected mice revealed 13 specific and reproducible nucleotide changes. These changes result in a sequence that matches the virulent CVB3/20 strain and are associated with promoting cardiovirulence. In contrast, we observed only one nucleotide change, low heart viral titers, and no heart and liver pathology in adult mice infected with CVB3/0(Adult). These results demonstrate that the aged host promotes rapid selection of a pathogenic variant of CVB3 from an avirulent strain and introduces a host-virus paradigm for studies of viral infection in the aged.

Aging↗

PubMed2006

Vitamin C deficiency increases the lung pathology of influenza virus-infected gulo-/- mice.

This study was designed to determine the effects of vitamin C deficiency on the immune response to infection with influenza virus. l-Gulono-gamma-lactone oxidase gene-inactivated mice (gulo-/- mice) require vitamin C supplementation for survival. Five-wk-old male and female gulo-/- mice were provided water or water containing 1.67 mmol/L vitamin C for 3 wk before inoculation with influenza A/Bangkok/1/79. There were no differences in lung influenza virus titers between vitamin C-adequate and -deficient mice; however, lung pathology in the vitamin C-deficient mice was greater at 1 and 3 d after infection but less at d 7 compared with vitamin C-adequate mice. Male vitamin C-deficient mice had higher expression of mRNA for regulated upon activation normal T expressed and secreted (RANTES), IL-1beta, and TNF-alpha in the lungs at d 1 after infection compared with male controls. However, at d 3 after infection, male vitamin C-deficient mice had less expression of mRNA for RANTES, monocyte chemotactic protein-1 (MCP-1), and IL-12 compared with male controls. None of these differences were observed in female mice. Vitamin C-deficient male mice also had greater nuclear factor-kappaB activation as early as 1 d after infection compared with male controls. These data suggest that vitamin C is required for an adequate immune response in limiting lung pathology after influenza virus infection.

Animals↗

PubMed2005

Diesel exhaust enhances influenza virus infections in respiratory epithelial cells.

Several factors, such as age and nutritional status, can affect the susceptibility to influenza infections. Moreover, exposure to air pollutants, such as diesel exhaust (DE), has been shown to affect respiratory virus infections in rodent models. Influenza virus primarily infects and replicates in respiratory epithelial cells, which are also a major targets for inhaled DE. Using in vitro models of human respiratory epithelial cells, we determined the effects of an aqueous-trapped solution of DE (DE(as)) on influenza infections. Differentiated human nasal and bronchial epithelial cells, as well as A549 cells, were exposed to DE(as) and infected with influenza A/Bangkok/1/79. DE(as) enhanced the susceptibility to influenza virus infection in all cell models and increased the number of influenza-infected cells within 24 h post-infection. This was not caused by suppressing antiviral mediator production, since interferon (IFN) beta levels, IFN-dependent signaling, and IFN-stimulated gene expression were also enhanced by exposure to DE(as). Many of the adverse effects induced by DE exposure are mediated by oxidative stress. Exposure to DE(as) used in these studies generated oxidative stress in respiratory epithelial cells, and addition of the antioxidant glutathione-ethylester (GSH-ET) reversed the effects of DE(as) on influenza infections. Furthermore, DE(as) increased influenza virus attachment to respiratory epithelial cells within 2 h post-infection. Taken together, the results presented here suggest that in human respiratory epithelial cells oxidative stress generated by DE(as) increases the susceptibility to influenza infection and that exposure to DE(as) increases the ability of the virus to attach to and enter respiratory epithelial cells.

Blotting, Western↗

PubMed2005

Benign coxsackievirus damages heart muscle in iron-loaded vitamin E-deficient mice.

Several oxidative stressors (dietary selenium deficiency, dietary vitamin E deficiency coupled with fish oil feeding, genetic reduction of glutathione peroxidase activity) allow a normally benign coxsackievirus B3 (CVB3/0) to damage heart muscle in host mice. This study investigated whether dietary iron overload, another oxidant stress, would also permit CVB3/0 to exert a cardiopathologic effect in vitamin E-deficient (-VE) mice. Four groups of mice were fed either a -VE or a +VE diet containing either an adequate or an excessive (30x) amount of iron. After 4 weeks of feeding, the mice were inoculated with CVB3/0 and heart damage was assessed at various times postinfection. Mice fed a diet sufficient in VE with excess iron developed heart damage equivalent to mice fed a diet deficient in vitamin E without excess iron. However, severe heart damage occurred in the group fed a diet deficient in VE with excess iron, which was the most pro-oxidative diet. The highest heart viral titers were found in mice fed the -VE/excessive iron diet. However, the extent of heart damage did not always correlate with the formation of TBARS in liver homogenates. Further research is needed to clarify the role of oxidative stress and iron overload in determining the course of viral infection.

Animals↗

PubMed2004

Host nutritional status: the neglected virulence factor.

The emergence of new infectious diseases and old diseases with new pathogenic properties is a burgeoning worldwide problem. Severe acute respiratory syndrome (SARS) and acquired immune deficiency syndrome (AIDS) are just two of the most widely reported recent emerging infectious diseases. What are the factors that contribute to the rapid evolution of viral species? Various hypotheses have been proposed, all involving opportunities for virus spread (for example, agricultural practices, climate changes, rainforest clearing or air travel). However, the nutritional status of the host, until recently, has not been considered a contributing factor to the emergence of infectious disease. In this review, we show that host nutritional status can influence not only the host response to the pathogen, but can also influence the genetic make-up of the viral genome. This latter finding markedly changes our concept of host-pathogen interactions and creates a new paradigm for the study of such phenomena.

Animals↗

PubMed2004

Unexpected hazard of illegal immigration: Outbreak of viral myocarditis exacerbated by confinement and deprivation in a shipboard cargo container.

We present a group of 18 illegal immigrant stowaways who arrived in a shipboard cargo container suffering from gastroenteritis, dehydration, and malnutrition and showing evidence of viral myocarditis in 3 of 4 fatalities. Our investigation included an evaluation of the 2-week ocean voyage, analysis of medical records and laboratory results of the survivors, autopsies on the decedents, and viral studies on their heart tissue. Of 3 stowaways who died shipboard, 2 showed lymphocytic myocarditis and 1 could not be evaluated histologically due to decomposition. A fourth stowaway died 4 months after arrival with dilated cardiomyopathy and lymphocytic myocarditis. Reverse-transcriptase polymerase chain reaction and nucleotide sequencing of viral isolates from the decedents' heart tissues demonstrated Coxsackie virus B3 genome. We believe that these cases represent an outbreak of viral myocarditis, exacerbated by acute dehydration and malnutrition, due to confinement within the shipping container. Our evidence indicates that close confinement promoted the spread of the virus, and nutritional deprivation increased the stowaways' vulnerability. Furthermore, our observations support the conclusion, based on experimental studies, that nutritionally induced oxidative stress increased the virulence of the etiologic viral agent. In summary, these cases represent a potential infectious disease hazard of illegal immigration.

Adolescent↗

PubMed2003

Coxsackievirus B3-resistant mice become susceptible in Se/vitamin E deficiency.

The severity of the heart damage caused by a coxsackievirus infection in mice is determined by several factors, including the genotype of the infecting virus as well as the genetic background of the infected host. Earlier work by us showed that the cardiovirulence of a given coxsackievirus genotype could be increased substantially by feeding the host a diet nutritionally deficient in either selenium or vitamin E. Here we report that host genetic background as a determinant of viral infection outcome is superseded by feeding the host a diet nutritionally deficient in both selenium and vitamin E. Mice of the C57Bl/6 strain, normally resistant to coxsackievirus B3-induced myocarditis, become susceptible when fed such a doubly deficient diet. Our results demonstrate the powerful influence of host nutritional status on the course of viral infection compared to other variables traditionally considered to play major roles in determining the extent of virally induced inflammatory heart disease.

Animals↗

PubMed2003

Selenium deficiency and viral infection.

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.

Animals↗

PubMed2002

A novel S-adenosyl-L-methionine:arsenic(III) methyltransferase from rat liver cytosol.

S-Adenosyl-l-methionine (AdoMet):arsenic(III) methyltransferase, purified from liver cytosol of adult male Fischer 344 rats, catalyzes transfer of a methyl group from AdoMet to trivalent arsenicals producing methylated and dimethylated arsenicals. The kinetics of production of methylated arsenicals in reaction mixtures containing enzyme, AdoMet, dithiothreitol, glutathione (GSH), and arsenite are consistent with a scheme in which monomethylated arsenical produced from arsenite is the substrate for a second methylation reaction that yields dimethylated arsenical. The mRNA for this protein predicts a 369-amino acid residue protein (molecular mass 41056) that contains common methyltransferase sequence motifs. Its sequence is similar to Cyt19, a putative methyltransferase, expressed in human and mouse tissues. Reverse transcription-polymerase chain reaction detects S-adenosyl-l-methionine:arsenic(III) methyltransferase mRNA in rat tissues and in HepG2 cells, a human cell line that methylates arsenite and methylarsonous acid. S-Adenosyl-l-methionine:arsenic(III) methyltransferase mRNA is not detected in UROtsa cells, an immortalized human urothelial cell line that does not methylate arsenite. Because methylation of arsenic is a critical feature of its metabolism, characterization of this enzyme will improve our understanding of this metalloid's metabolism and its actions as a toxin and a carcinogen.

Amino Acid Sequence↗