Coxsackievirus B3 (CVB3) is nonenveloped and has a single-stranded positive-sense RNA genome. CVB3 induces myocarditis and ultimately dilated cardiomyopathy. Although there are mounting evidences of an interaction between CVB3 particles and the cellular receptors, coxsackievirus and adenovirus receptor (CAR) and decay-accelerating factor (DAF), very little is known about the mechanisms of internalization and trafficking. In the present study, we used the CVB3 H3 strain, which is CAR-dependent but DAF-independent Woodruff variant and found that during entry, CVB3 particles were colocalized in clathrin, after interacting primarily with CAR, which was not recycled to the plasma membrane. We also found that CVB3 internalization was dependent on the function of dynamin, a large GTPase that has an essential role in endocytosis. Heat-shock cognate protein, Hsc70, which acts as a chaperone in the release of coat proteins from clathrin-coated vesicles (CCV), played a role in CVB3 trafficking processes. Moreover, endosomal acidification was crucial for CVB3 endocytosis. Finally, CVB3 was colocalized in early endosome autoantigen 1 (EEA1) molecules, which are involved in endosome-endosome tethering and fusion. In conclusion, these data together indicate that CVB3 uses clathrin-mediated endocytosis and is transcytosed to early endosomes.

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Coxsackievirus B3 (CVB3), an enterovirus in the Picornavirus family, is the most common human pathogen associated with myocarditis and idiopathic dilated cardiomyopathy. We found upregulation of the cysteine-rich protein gene (cyr61) after CVB3 infection in HeLa cells with a cDNA microarray approach, which is confirmed by Northern blot analysis. It is also revealed that the extracellular amount of Cyr61 protein was increased after CVB3 infection in HeLa cells. cyr61 is an early-transcribed gene, and the Cyr61 protein is secreted into the extracellular matrix. Its function is related to cell adhesion, migration, and neuronal cell death. Here, we show that activation of the cyr61 promoter by CVB3 infection is dependent on JNK activation induced by CVB3 replication and viral protein expression in infected cells. To explore the role of Cyr61 protein in infected HeLa cells, we transiently overexpressed cyr61 and infected HeLa cells with CVB3. This increased CVB3 growth in the cells and promoted host cell death by viral infection, whereas down-expression of cyr61 with short interfering RNA reduced CVB3 growth and showed resistance to cell death by CVB3 infection. In conclusion, we have demonstrated a new role for cyr61 in HeLa cells infected with CVB3, which is associated with the cell death induced by virus infection. These data thus expand our understanding of the physiological functions of cyr61 in virus-induced cell death and provide new insights into the cellular factors involved.

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Background: Although human adenovirus-36 (Ad-36) has been reported to be associated with obesity in US adults and children, Korean children and the Italian population, the association has not been found in Dutch or Belgian populations or in US military subjects. Therefore, we examined whether Ad-36 infection is associated with obesity in Korean adults. Methods: A total of 540 age-and sex-matched individuals, who were normal weight, overweight or obese, were selected from participants in routine health examinations at the Ewha Womans University Medical Center. Overweight participants were defined as those with a body mass index (BMI) of 23pBMIo25 kg m À2 and obese subjects were those with BMIX25 kg m À2 , according to the International Obesity Task Force definition. Ad-36 antibody was measured using a serum neutralization assay. Results: Although more overweight participants than normal or obese subjects tested positive for the Ad-36 antibody (40%, 32.8% and 30%, respectively), the differences were not significant. The participants who tested positive for Ad-36 antibody had lower levels of triglycerides (TG) in each of the three groups, higher total cholesterol (TC) in the obese group and higher highdensity lipoprotein-cholesterol (HDL-C) in both the normal and obese groups. The odds ratio (OR) for Ad-36 antibody positivity was greater in overweight than in normal subjects (OR ¼ 2.03; 95% confidence interval (CI), 1.16-3.55) after adjusting for age, sex and waist circumference. However, this OR was non-significant in the obese group (OR ¼ 1.56; 95% CI, 0.67-3.67).

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