Geographical distribution of hepatitis C virus genotypes in blood donors:an international collaborative survey

The frequency of infection with the six classified major genotypes of hepatitis C virus (HCV) was investigated in 447 infected volunteer blood donors from the following nine countries: Scotland, Finland, The Netherlands, Hungary, Australia, Egypt, Japan, Hong Kong, and Taiwan. Viral sequences in plasma from blood donors infected with HCV were amplified in the 5'-noncoding region and were typed by restriction fragment length polymorphism analysis. Electrophoresis of DNA fragments produced by cleavage with HaeIII-RsaI and ScrFI-HinfI allowed HCV types 1 (or 5), 2, 3, 4, and 6 to be identified. Further analysis with MvaI-HinfI allowed sequences of the type 5 genotype to be distinguished from sequences of type 1 genotype. Types 1, 2, and 3 accounted for almost all infections in donors from Scotland, Finland, The Netherlands, and Australia. Types 2 and 3 were not found in the eastern European country (Hungary), where all but one of the donors were infected with type 1. Donors from Japan and Taiwan were infected only with type 1 or 2, while types 1, 2, and 6 were found in those from Hong Kong. HCV infection among Egyptians was almost always by type 4. Donors infected with HCV type 1 showed broad serological reactivity with all four antigens of the second generation Chiron RIBA-2 assay (Chiron Corporation, Emeryville, Calif.), while infection with divergent HCV genotypes elicited antibodies mainly reactive to c22-3 and c33c. Reactivities with antibodies 5-1-1 and c100-3 were infrequent and were generally weak, irrespective of the geographical origin of the donor. Because the envelope region of HCV is even more variable than the NS-4 region, it is likely that vaccines based on these proteins need to be multivalent and perhaps specifically adapted for different geographical regions.link_to_subscribed_fulltex

Hepatitis C virus genotype frequency in Isfahan province of Iran: a descriptive cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Hepatitis C is an infectious disease affecting the liver, caused by the hepatitis C virus (HCV). The hepatitis C virus is a small, enveloped, single-stranded, positive sense RNA virus with a large genetic heterogeneity. Isolates have been classified into at least eleven major genotypes, based on a nucleotide sequence divergence of 30-35%. Genotypes 1, 2 and 3 circulate around the world, while other genotypes are mainly restricted to determined geographical areas. Genotype determination of HCV is clinically valuable as it provides important information which can be used to determine the type and duration of therapy and to predict the outcome of the disease.</p> <p>Results</p> <p>Plasma samples were collected from ninety seven HCV RNA positive patients admitted to two large medical laboratory centers in Isfahan province (Iran) from the years 2007 to 2009. Samples from patients were subjected to HCV genotype determination using a PCR based genotyping kit. The frequency of HCV genotypes was determined as follows: genotype 3a (61.2%), genotype 1a (29.5%), genotype 1b (5.1%), genotype 2 (2%) and mixed genotypes of 1a+3a (2%).</p> <p>Conclusion</p> <p>Genotype 3a is the most frequent followed by the genotype 1a, genotype 1b and genotype 2 in Isfahan province, Iran.</p

Determinants of online shopping among tertiary students in Ghana: An extended technology acceptance model

The increasing penetration rate of the internet and technology in the world is quickly promoting online shopping. This has been fueled by growing innovations in the telecommunication and financial sector in an attempt to depeen financial inclusion. Innovations such as mobile money payments systems by mobile telephony companies have contributed to the continuous growth in online shopping amidst and the new generation of consumers who desire richer experiences. This study sought to identify the determinants of online shopping behaviour among tertiary students through the lens of the Technology Acceptance Model (TAM). The study proposed a revised TAM that integrated perceived cost and perceived risk to investigate what determined students online shopping intention and actual use. The survey involved a sample of 580 undergraduate students. The statistical technique used was Structural Equation Modelling-Partial Least Squares (SEM-PLS). The results showed that effect of ease of use on usefulness was very significant as same has been predicted by the Technology Acceptance Model. Among the independent variables, perceived cost (PC) was found to be the most significant factor affecting actual use (AU) of online shopping among students, nonetheless, perceived cost (PC) had no significant effect on purchase intention (PI). Perceived risk (PR) had no significant effect on actual use (AU) however, had a significant effect on purchase intention (PI). The study recommends online sellers to make online shopping efficient and less costive with assured safety and security of transactions as well as the product itself. A set of shopping platform could even be created specifically to give discounts and other offers to students. It also recommends future studies to employ additional determining factors such as the type of product/service, convenience and personal/demographic and geographic factors as influential to students’ online purchasing behaviour. © 2019, © 2019 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license

Lysosomotropic agents as HCV entry inhibitors

HCV has two envelop proteins named as E1 and E2 which play an important role in cell entry through two main pathways: direct fusion at the plasma membrane and receptor-mediated endocytosis. Fusion of the HCV envelope proteins is triggered by low pH within the endosome. Lysosomotropic agents (LA) such as Chloroquine and Ammonium chloride (NH4Cl) are the weak bases and penetrate in lysosome as protonated form and increase the intracellular pH. To investigate the antiviral effect of LA (Chloroquine and NH4Cl) on pH dependent endocytosis, HCV pseudoparticles (HCVpp) of 1a and 3a genotype were produced and used to infect liver cells. The toxicological effects of Chloroquine and NH4Cl were tested in liver cells through MTT cell proliferation assay. For antiviral screening of Chloroquine and NH4Cl, liver cells were infected with HCVpp of 3a and 1a genotype in the presence or absence of different concentrations of Chloroquine and NH4Cl and there luciferase activity was determined by using a luminometer. The results demonstrated that Chloroquine and NH4Cl showed more than 50% reduction of virus infectivity at 50 μM and 10 mM concentrations respectively. These results suggest that inhibition of HCV at fusion step by increasing the lysosomal pH will be better option to treat chronic HCV

Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region

Hepatitis C virus (HCV) shows substantial nucleotide sequence diversity distributed throughout the viral genome, with many variants showing only 68 to 79 % overall sequence similarity to one another. Phylogenetic analysis ofnucleofide sequences derived from part of the gene encoding a non-structural protein (NS-5) has provided evidence for six major genotypes of HCV amongst a worldwide collection of 76 samples from HCV-infected blood donors and patients with chronic hepatitis. Many of these HCV types comprised a number of more closely related subtypes, leading to a current total of 11 genetically distinct viral populations. Phylo-genetic analysis of other regions of the viral genome produced relationships between published sequences equivalent to those found in NS-5, apart from the more highly conserved 5 &apos; non-coding region in which only the six major HCV types, but not subtypes, could be differentiated. A new nomenclature for HCV variants is proposed in this communication that reflects the twotiered nature of sequence differences between different viral isolates. The scheme classifies all known HCV variants to date, and describes criteria that would enable new variants to be assigned within the classification as they are discovered

Serum Islet Cell Autoantibodies During Interferon α Treatment in Patients With HCV-Genotype 4 Chronic Hepatitis

Chronic hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease worldwide and HCV genotype 4 (HCV4) is predominant in African and Middle Eastern countries. It is well established that interferon-α (IFNa) treatment for HCV may trigger serum autoantibodies against pancreatic islet cells (ICA) in a subgroup of patients. Available data on the incidence of ICA during IFNa therapy for chronic HCV4 infection are not conclusive. We investigated the appearance of ICA in 40 naïve Egyptian patients (38 males, 32 ± 6 years) with histologically defined chronic HCV4 infection undergoing IFNa treatment at a dose of 9-million U/week for 24 weeks. Serum samples were collected at baseline and following IFNa therapy and ICA were detected using indirect immunofluorescence. Baseline evaluation indicated that 2/40 (5%) patients had detectable serum ICA. After the completion of the treatment scheme, 12/38 (32%) previously ICA negative patients became ICA positive; however, no patient developed impaired glucose tolerance (IGT) or diabetes during follow-up. In conclusion, we submit that IFNa treatment for chronic hepatitis C (CHC) may induce serum ICA in one-third of Egyptian patients with HCV4. These autoantibodies, however, do not lead to alterations in glucose metabolism

siRNAs: Potential therapeutic agents against Hepatitis C Virus

Hepatitis C virus is a major cause of chronic liver diseases which can lead to permanent liver damage, hepatocellular carcinoma and death. The presently available treatment with interferon plus ribavirin, has limited benefits due to adverse side effects such as anemia, depression and "flu-like" symptoms. Needless to mention, the effectiveness of interferon therapy is predominantly, if not exclusively, limited to virus type 3a and 3b whereas in Europe and North America the majority of viral type is 1a and 2a. Due to the limited efficiency of current therapy, RNA interference (RNAi) a novel regulatory and powerful silencing approach for molecular therapeutics through a sequence-specific RNA degradation process represents an alternative option. Several reports have indicated the efficiency and specificity of synthetic and vector based siRNAs inhibiting HCV replication. In the present review, we focused that combination of siRNAs against virus and host genes will be a better option to treat HC

The Evolution of the Major Hepatitis C Genotypes Correlates with Clinical Response to Interferon Therapy

Patients chronically infected with hepatitis C virus (HCV) require significantly different durations of therapy and achieve substantially different sustained virologic response rates to interferon-based therapies, depending on the HCV genotype with which they are infected. There currently exists no systematic framework that explains these genotype-specific response rates. Since humans are the only known natural hosts for HCV-a virus that is at least hundreds of years old-one possibility is that over the time frame of this relationship, HCV accumulated adaptive mutations that confer increasing resistance to the human immune system. Given that interferon therapy functions by triggering an immune response, we hypothesized that clinical response rates are a reflection of viral evolutionary adaptations to the immune system.We have performed the first phylogenetic analysis to include all available full-length HCV genomic sequences (n = 345). This resulted in a new cladogram of HCV. This tree establishes for the first time the relative evolutionary ages of the major HCV genotypes. The outcome data from prospective clinical trials that studied interferon and ribavirin therapy was then mapped onto this new tree. This mapping revealed a correlation between genotype-specific responses to therapy and respective genotype age. This correlation allows us to predict that genotypes 5 and 6, for which there currently are no published prospective trials, will likely have intermediate response rates, similar to genotype 3. Ancestral protein sequence reconstruction was also performed, which identified the HCV proteins E2 and NS5A as potential determinants of genotype-specific clinical outcome. Biochemical studies have independently identified these same two proteins as having genotype-specific abilities to inhibit the innate immune factor double-stranded RNA-dependent protein kinase (PKR).An evolutionary analysis of all available HCV genomes supports the hypothesis that immune selection was a significant driving force in the divergence of the major HCV genotypes and that viral factors that acquired the ability to inhibit the immune response may play a role in determining genotype-specific response rates to interferon therapy