Bile acids promote the expression of hepatitis C virus in replicon-harboring cells. (1/15)

Hepatitis C virus (HCV) is a cause of chronic liver disease, with more than 170 million persistently infected individuals worldwide. Although the combination therapy of alpha interferon (IFN-alpha) and ribavirin is effective for chronic HCV infection, around half of all patients infected with HCV genotype 1 fail to show sustained virologic responses and remain chronically infected. Previously, we demonstrated that bile acids were essential for growth of porcine enteric calicivirus in cell culture in association with down-regulation of IFN responses. Because hepatocytes are exposed to high concentrations of bile acids in the liver, we hypothesized that bile acids have similar effects on HCV replication. We incubated HCV replicon-harboring cells (genotype 1b, Con1) in the presence of various bile acids and monitored the expression of HCV RNA and protein (NS5B). The addition of an individual bile acid (deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, or glycochenodeoxycholic acid) in the medium increased the levels of HCV RNA and proteins up to fivefold at 48 h of incubation. An antagonist of bile acid receptor farnesoid X receptor (FXR), Z-guggulsterone, reduced the bile acid-mediated increase of HCV RNA. When IFN (alpha or gamma) and each bile acid were incubated together, we observed that bile acid significantly reduced the anti-HCV effect of IFN. These results indicated that bile acids are factors in the failure of IFN treatment for certain patients infected with HCV genotype 1. Our finding may also contribute to the establishment of better regimens for treatment of chronic HCV infections by including agents altering the bile acid-mediated FXR pathway.  (+info)

Proteins induced by infection with caliciviruses. (2/15)

Three polypeptides with mol. wt. 100 (P100), 80 (P80) and 65 (P65) X 10(3) were found in calicivirus infected cells. P100 and P80 were present in sub-molar amounts compared with P65 and no precursor product relationship between the three polypeptides could be demonstrated using pulse-chase experiments or selective inhibitors of protein synthesis and of proteases. In the presence of protease inhibitors a polypeptide with mol. wt. 120 X 10(3) (P120) was demonstrated which appeared to be the precursor of P100. Possible mechanisms of translation in the caliciviruses are discussed.  (+info)

Vesicular exanthema of swine virus: isolation and serotyping of field samples. (3/15)

Virus isolation was attempted from 262 field samples of vesicular material collected during the outbreaks of vesicular exanthema of swine in the U.S.A. from 1952-54. Using primary swine kidney culture, viral cytopathogenic agents were isolated from 76.3% of the samples. However, an overall recovery rate of 82.1% was obtained after samples negative in tissue culture were inoculated intradermally in susceptible swine. All vesicular exanthema of swine virus isolates were identified as serotype B51 using complement fixation and serum neutralization tests. Two isolates did not react with antisera to known vesicular agents of swine and failed to produce vesicles or clinical signs of disease upon inoculation in swine. One vesicular exanthema of swine virus isolate from tissue of equine origin was pathogenic for swine but produced limited vesiculation at the site of intradermalingual inoculation in the tongue of a pony infected experimentally. Type B51 virus was reisolated from lesions produced in the pony and the pony became seropositive for virus type B51.  (+info)

Swine vesicular disease: virological studies of experimental infections produced by the England-72 virus. (4/15)

Pigs exposed to relatively small amounts of virus by intradermal inoculation of the feet or by skin sacrification developed clinical disease. Large amounts of virus were recovered from samples taken from the nose, mouth, pharynx, rectum and the prepuce or vagina during the first week of infection and smaller amounts during the second week. Virus was recovered from the faeces of most animals 16 days after infection and from one animal for 23 days. Pigs in contact with inoculated animals were killed at intervals before the appearance of clinical disease. The distribution and amounts of virus in various tissues indicated that infection has most likely gained entry through the skin or the epithelia and mucosae of the digestive tract. Some pigs acquired subclinical infections in which no virus excretion was detected and no transmission of infection to susceptible pigs took place over a period of 5 weeks.  (+info)

Swine vesicular disease: attempts to transmit infection to cattle and sheep. (5/15)

Cattle and sheep were housed with infected pigs for 11 days. Small amounts of virus were recovered intermittently from the pharynx, milk and rectal swabs of the cattle, but no evidence of subclinical infection was found. Some indication of virus growth in the sheep was obtained in that large amounts of virus were recovered from the pharyngeal region 4 to 7 days after exposure and six of the eight sheep developed significant titres of neutralizing antibody which were maintained in four animals for at least 6 weeks.  (+info)

Attemps to infect pigs with Coxsackie virus type B5. (6/15)

Despite the existence of a close serological relationship between the enteroviruses Swine Vesicular Disease (SVD) and Coxsackie type B5 (Cx B5), the administration of this Coxsackie virus type to susceptible pigs by various routes failed to produce clinical disease.Viraemia was not detected after exposure but virus was recovered intermittently from faeces and buccal swabs. A mixed virus population was demonstrated in faecal cultures from some pigs, including Coxsackie virus type B5 and other agents, presumably native pig enteroviruses. The Coxsackie virus persisted in faeces in declining amounts for up to 8 days after primary exposure.Serum neutralizing antibody showed a transient rise to Coxsackie virus, reaching a peak at 14 days and declining below demonstrable titres by 28 days after exposure. The antibody titres attained were proportional to the dose of virus administered and the degree of neutralization was very similar to both SVD and Cx B5 viruses.On cross challenge by exposure to SVD virus 28 days after exposure to Cx B5 virus, most animals (5/6) succumbed with typical vesicular lesions, although the serum neutralizing antibody titres showed a characteristically anamnestic response to both viruses.  (+info)

Swine vesicular disease: comparative studies of viruses isolated from different countries. (7/15)

Seven viruses isolated from outbreaks of swine vesicular disease in various countries between 1966 and 1973 were compared in pigs and infant mice. All produced a similar disease and virus excretion pattern in the pig, although the Italy/66 virus was considerably less virulent than the other viruses. The results of cross neutralization tests of convalescent pig sera and the response of 5-day-old mice to intraperitoneal inoculation indicated minor differences between some viruses. The Italy/66, Hong Kong/71 and France/73 viruses differed from each other and also from the Italy/72, England/72, Austria/73 and Poland/73 group of viruses.  (+info)

A model for vesicular exanthema virus, the prototype of the calicivirus group. (8/15)

The structure of vesicular exanthema virus, the prototype member of the calicivirus group, has been studied in more detail. The RNA comprises 18% of mol. wt. of about 2.8 x 10(6), based on polyacrylamide gel electrophoresis experiments in the presence of formaldehyde. The virus contains one major polypeptide, mol. wt. 70 x 10(3) as determined by polyacrylamide gel electrophoresis and by chromatography on Sepharose 6B in the presence of 6 M-guanidine. Further evidence for the presence of a single major polypeptide was obtained by tryptic peptide analysis of 35S-methionine labelled virus. The mol. wt. of a protein oligomer produced by adjusting the pH of virus suspensions to 3.5 was c. 200 x 10(3). On the basis of these data we propose a T = 3 model for the virus capsid incorporating 180 copies of the virus protein.  (+info)