ABSTRACT
Different extracts of leaf parts of Wrightia tinctoria and fruit powder of Morinda citrifolia have been studied against replication of HIV-1(IIIB) in MT-4 cells and HCV in Huh 5.2 cells. Chloroform extract of Wrightia tinctoria exhibited a maximum protection of 48% against the cytopathic effect of HIV-1(IIIB) in MT-4 cells. Fruit juice of Morinda citrifolia exhibited a displayed marked cytotoxic activity in lymphocyte (MT-4) cells (CC50: 0.19 mg/ml). The 50% effective concentration for inhibition of HCV subgenomic replicon replication in Huh 5-2 cells by Morinda citrifolia was 0.98 mug/ml and by chloroform extract of Wrightia tinctoria was 10 mug/ml. The concentration that reduced the growth of exponentially proliferating Huh 5-2 cells by 50% was greater than 50 mug/ml.
ABSTRACT
4-[(1,2-dihydro-2-oxo-3H-indol-3-ylidene)amino]-N(4,6-dimethyl-2-pyrimidiny)benzene sulphonamide and its derivatives were evaluated for antiviral activity against Pathogenic viruses such as Hepatitis C Virus and SARS-CoV in Vero and Huh 5-2 cells, respectively. The 5-fluoro derivative inhibited the HCV RNA synthesis at 6 mug/ml, without toxicity at a concentration up to 42 mug/ml in Huh 5-2 cells. Among the compounds tested SPIII-5F exhibits the 45% maximum protection against replication of SARS-CoV in Vero cells.
ABSTRACT
Non-human adenoviruses such as bovine adenovirus type 3 (BAV-3) that do not replicate in human cells but can infect human cells in culture could provide an attractive alternative to human adenoviral vectors for gene therapy. In addition, a large-animal model for genetic diseases can be very useful for the assessment of the efficacy of adenovector-mediated gene delivery in man. Recombinant human subgroup C adenovectors use the coxsackie and adenovirus receptor (CAR) to enter their target cells. Through RT-PCR and sequencing we determined the complete coding sequence of bovine CAR which serves as the primary adenoviral attachment site on bovine cells. A multiple sequence alignment, involving all the previously identified CAR species (man, mouse, rat, pig, and dog) showed that bovine CAR was most related to porcine CAR (92% nucleotide similarity) and demonstrated a highly conserved adenovirus binding Ig1 domain.
Subject(s)
Receptors, Virus/chemistry , Receptors, Virus/genetics , Amino Acid Sequence , Animals , Cattle , Cloning, Molecular , Conserved Sequence , Coxsackie and Adenovirus Receptor-Like Membrane Protein , DNA, Complementary/genetics , Genetic Therapy/veterinary , Humans , Mastadenovirus/genetics , Mastadenovirus/metabolism , Molecular Sequence Data , Protein Structure, Tertiary , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Virus/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sequence Alignment , Sequence HomologyABSTRACT
The inflammatory bowel diseases (IBD), Crohn's disease (CD), and ulcerative colitis (UC), are complex multifactorial traits involving both environmental and genetic factors. Mannan-binding lectin (MBL) plays an important role in non-specific immunity and complement activation. Point mutations in codons 52, 54 and 57 of exon 1 of the MBL gene are associated with decreased MBL plasma concentrations and increased susceptibility to various infectious diseases. If these MBL mutations could lead to susceptibility to putative IBD-etiological microbial agents, or could temper the complement-mediated mucosal damage in IBD, MBL could function as the link between certain microbial, immunological and genetic factors in IBD. In this study, we investigated the presence of the codon 52, 54 and 57 mutations of the MBL gene in 431 unrelated IBD patients, 112 affected and 141 unaffected first-degree relatives, and 308 healthy control individuals. In the group of sporadic IBD patients (n = 340), the frequency of the investigated MBL variants was significantly lower in UC patients when compared with CD patients (P = 0.01) and with controls (P = 0.02). These results suggest that MBL mutations which decrease the formation of functional MBL could protect against the clinical development of sporadic UC, but not of CD. This could be explained by the differential T-helper response in both diseases.
Subject(s)
Carrier Proteins/genetics , Colitis, Ulcerative/genetics , Crohn Disease/genetics , Polymorphism, Genetic/genetics , Adolescent , Adult , Child , Colitis, Ulcerative/pathology , Collectins , Crohn Disease/pathology , DNA Mutational Analysis , Female , Gene Frequency/genetics , Genetic Predisposition to Disease/genetics , Genotype , Humans , Male , Middle Aged , Phenotype , Point Mutation/genetics , Polymerase Chain ReactionABSTRACT
The inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC) are complex multifactorial traits involving both environmental and genetic factors. Recent studies have shown the important role of pro-inflammatory cytokines and chemokines, including RANTES, in IBD. RANTES is the natural ligand for the CC-chemokine receptor 5 (CCR5). The chromosomal location of the CCR5 gene on 3p21 coincides with an IBD-susceptibility locus identified by genome-wide scanning. A 32-bp deletion (A32) in the CCR5 gene results in a nonfunctional receptor and is found with high frequency in Caucasians. In this study, we investigated the presence of the CCR5delta32 allele in a large cohort of IBD patients and in a healthy control population. Blood samples were obtained from 538 unselected IBD cases (433 unrelated IBD patients: 289 CD, 142 UC, 2 indeterminate colitis; 105 affected first-degree relatives) and 135 unaffected first-degree family members. Of the IBD patients, 36% had familial IBD with at least two members being affected. There were no significant differences in the CCR5delta32 mutation frequency between IBD patients and healthy controls, nor between CD and UC patients. There was no correlation between the CCR5delta32 genotype and the age at IBD-diagnosis, the frequency of surgical intervention, or disease localization. Only the association between CCR5delta32 homozygosity and the presence of anal lesions in CD patients was statistically significant (P=0.007). Analysis by the transmission/disequilibrium test showed no significant transmission distortion to the probands or their clinically silent siblings. Based on these results, it is unlikely that the CCR5delta32 allele is an important marker for predisposition to IBD.
Subject(s)
Inflammatory Bowel Diseases/genetics , Receptors, CCR5/genetics , Sequence Deletion , Adolescent , Adult , Alleles , Child , Child, Preschool , DNA/genetics , Family Health , Female , Gene Frequency , Genotype , Humans , Male , Middle Aged , Polymorphism, GeneticABSTRACT
Polymorphisms of the chemokine receptor genes CCR5 and CCR2 are associated with resistance to HIV-1 infection or delayed progression to AIDS. Few data are available on their combined prevalence in healthy subjects; we therefore examined the occurrence of CCR5-Delta32 and CCR2-64I polymorphisms in a sample of 310 healthy Belgians. Allele frequencies were 0.119 and 0.074 for CCR5-Delta32 and CCR2-64I, respectively. Genotype distributions for both polymorphisms were found to be in accordance with Hardy-Weinberg equilibrium, but a significant (p = 0.002) linkage disequilibrium between CCR5-Delta32 and CCR2-64I was observed. The high prevalence of CCR5-Delta32 and CCR2-64I in Belgians may need to be taken into account in the design of studies of antiretroviral treatments.
