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Scotomas in molecular virology and epidemiology of hepatitis C virus.

ABSTRACT: In the 1970s, scientists learned of a new pathogen causing non-A, non-B hepatitis. Classical approaches were used to isolate and characterize this new pathogen, but it could be transmitted experimentally only to chimpanzees and progress was slow until the pathogen was identified as hepatitis C virus (HCV) in 1989. Since then, research and treatment of HCV have expanded with the development of modern biological medicine: HCV genome organization and polyprotein processing were delineated in 1993; the first three-dimensional structure of HCV nonstructural protein (NS3 serine protease) was revealed in 1996; an infectious clone of HCV complementary DNA was first constructed in 1997; interferon and ribavirin combination therapy was established in 1998 and the therapeutic strategy gradually optimized; the HCV replicon system was produced in 1999; functional HCV pseudotyped viral particles were described in 2003; and recombinant infectious HCV in tissue culture was produced successfully in 2005. Recently, tremendous advances in HCV receptor discovery, understanding the HCV lifecycle, decryption of the HCV genome and proteins, as well as new anti-HCV compounds have been reported. Because HCV is difficult to isolate and culture, researchers have had to avail themselves to the best of modern biomedical technology; some of the major achievements in HCV research have not only advanced the understanding of HCV but also promoted knowledge of virology and cellular physiology. In this review, we summarize the advancements and remaining scotomas in the molecular virology and epidemiology of HCV.

SUBMITTER: Wang Y

PROVIDER: S-EPMC3848139 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Scotomas in molecular virology and epidemiology of hepatitis C virus.

Wang Yue Y

World journal of gastroenterology 20131101 44

In the 1970s, scientists learned of a new pathogen causing non-A, non-B hepatitis. Classical approaches were used to isolate and characterize this new pathogen, but it could be transmitted experimentally only to chimpanzees and progress was slow until the pathogen was identified as hepatitis C virus (HCV) in 1989. Since then, research and treatment of HCV have expanded with the development of modern biological medicine: HCV genome organization and polyprotein processing were delineated in 1993; ...[more]

PMID: 24307785

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Project description:There is an increased demand for molecular and epidemiological information regarding Hepatitis B Virus (HBV) infection as the disease severity depends on these specifications. We have aimed to analyze nucleos(t)ide analogues (NA) resistance and typical HBsAg escape mutations with the dispersion of HBV genotype/subgenotype/HBsAg serotypes on overlapping pol/S gene regions in the Turkish population. Samples were collected in Northern Cyprus. Reverse transcriptase (rt) region between 80-250 amino acids were amplified. Typical HBsAg escape mutations were determined as HBIg escape (6.48%), vaccine escape (8.34%), HBsAg misdiagnosis (9.25%), and immune escape mutations (8.34%). NAs resistances were determined as primary (2.78%), partial (2.78%), and compensatory mutations (26.85%) in overlapping pol/S gene region. The study patients were predominantly infected with HBV genotype D/D1 (98%). However, the predominant HBsAg serotype was ayw2 (99%). The most common NA resistance mutation was rtQ215H/P/S (16.67%), however, for S gene the misdiagnosis mutations were observed most frequently (9.25%). We can conclude that HBV D/D1 is the dominant strain and ayw2 is the dominant serotype in the Turkish Cypriot. Cyprus is an island located in the Eastern Mediterranean region, and it is, therefore, a key location for human trafficking and immigration; as a result of this reputation, it is necessary to analyze HBV phylogenetically for local dynamics, and our results indicate that treatment naïve population is prone to these pol/S gene mutations. However, if HBV strains were also analyzed among Greek Cypriots too, this would enable a complete island survey. With this work, we believe that we have enlightened this subject for further research.There is an increased demand for molecular and epidemiological information regarding Hepatitis B Virus (HBV) infection as the disease severity depends on these specifications. We have aimed to analyze nucleos(t)ide analogues (NA) resistance and typical HBsAg escape mutations with the dispersion of HBV genotype/subgenotype/HBsAg serotypes on overlapping pol/S gene regions in the Turkish population. Samples were collected in Northern Cyprus. Reverse transcriptase (rt) region between 80–250 amino acids were amplified. Typical HBsAg escape mutations were determined as HBIg escape (6.48%), vaccine escape (8.34%), HBsAg misdiagnosis (9.25%), and immune escape mutations (8.34%). NAs resistances were determined as primary (2.78%), partial (2.78%), and compensatory mutations (26.85%) in overlapping pol/S gene region. The study patients were predominantly infected with HBV genotype D/D1 (98%). However, the predominant HBsAg serotype was ayw2 (99%). The most common NA resistance mutation was rtQ215H/P/S (16.67%), however, for S gene the misdiagnosis mutations were observed most frequently (9.25%). We can conclude that HBV D/D1 is the dominant strain and ayw2 is the dominant serotype in the Turkish Cypriot. Cyprus is an island located in the Eastern Mediterranean region, and it is, therefore, a key location for human trafficking and immigration; as a result of this reputation, it is necessary to analyze HBV phylogenetically for local dynamics, and our results indicate that treatment naïve population is prone to these pol/S gene mutations. However, if HBV strains were also analyzed among Greek Cypriots too, this would enable a complete island survey. With this work, we believe that we have enlightened this subject for further research.

Project description:BackgroundHepatitis B virus (HBV) infection remains a serious global health challenge. The widespread distribution of HBV is highlighted by multiple HBV genotypes associated with different geographical origin and transmission patterns, as well as, clinical outcomes. Investigating population HBV genotype composition and origin is therefore highly warranted.MethodsIn this molecular epidemiological study we analysed 1157 HBV S-gene sequences collected from patients in Norway, primarily in the period 2004-2011, and linked them to epidemiological data from the Norwegian surveillance system for communicable diseases.ResultsOf the patients with reported country of infection (n = 909), 10% (n = 93) were infected in Norway, but the majority (n = 816; 90%) stated that they became infected outside of Norway. Of the patients infected outside of Norway, most became infected in Southeast and East Asia (n = 465; 51%) and Central, West, and North Africa (n = 254; 28%). The distribution of HBV genotypes in Norway is dominated by genotype D (32%) followed by genotype A (22%), B and C (18 and 18%, respectively), and E (7%). Genotype B, C and E were phylogenetically categorized by a majority of sequences originating from distinct geographical regions, either Asia or Africa, whereas genotype A and D originated from multiple geographic regions. However, within genotype A and D, our molecular epidemiology analysis indicated a geographical clustering of sequences depending on their geographical origin.ConclusionsThe majority of HBV patients in Norway became infected outside of Norway and were represented by most common genotypes. Patients stated to have been infected in Norway were found primarily within genotype A and D, and were phylogenetically characterized by both small local clusters and interspersed sequences that clustered with non-Norwegian sequences, indicating that a proportion of the patients assumed to have been infected in Norway likely became infected outside of Norway although assumed the contrary.

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Scotomas in molecular virology and epidemiology of hepatitis C virus.

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Scotomas in molecular virology and epidemiology of hepatitis C virus.

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