Knowledge of the specific functions of protein domains encoded by the genome of the hepatitis c virus hcv, a major human pathogen that contributes to liver disease worldwide, remains limited to insight from smallscale studies. Intrahost evolutionary dynamics of the hepatitis c virus. Hepatitis c virus hcv infection afflicts more than 170 million people worldwide, with the great majority of patients with acute hepatitis c developing chronic hcv infection. Hepatitis c genotypes viral hepatitis and liver disease. Anders olsona, shuhua cheng, chungyen ling, tingting wua, and ren suna,c,h,1. It causes acute hepatitis with a high propensity for chronic infection.
A comprehensive functional map of the hepatitis c virus. Hepatitis c virus hcv is an enveloped, singlestranded rna virus that has been classified in the flaviviridae family. When signs and symptoms are present, they may include jaundice, along with fatigue, nausea, fever and muscle aches. Hepatitis c virus hcv causes acute and chronic hepatitis which can eventually lead to permanent liver damage, hepatocellular carcinoma and death. Distribution of hepatitis c virus genotypes in a diverse us integrated health care population. Structure, genomic organization, replication and variability of. The hcv particles are spherical and heterogenous in size, typically ranging 4080 nm in diameter. Hepatitis c is an infectious disease caused by a virus.
The hcv genome is a linear molecule with a length of approximately 9. Hepatitis a is caused by a virus in the picornavirus family. Figure 2 the mechanisms of hcv persistence in liver cells. The hepatitis c virus is a single stranded, enveloped, positive sense rna virus. Flaviviruses figure 5 are icosahedral, positive strand rna viruses and gain an envelope from their host cell. Genetic organization of the hepatitis b virus genome. The exact stage and mech anism by which the viral genome is released. Its genome is a single stranded rna molecule of positivestrand polarity of 7478 bases.
Today, most people become infected with the hepatitis c virus by sharing needles or other equipment to inject drugs. Nainan ov, alter, mj, kruszonmoran d, gao fx, xia g, mcquillan g margolis hs. Pathogenesis, natural history, treatment, and prevention. Pathogenesis, natural history, treatment, and prevention of. Phylogenetic analysis of fulllength or partial sequences ofhcv strains isolated in various regionsof the world has led to the identi. The hepatitis c virus hcv is a small 5565 nm in size, enveloped, positivesense singlestranded rna virus of the family flaviviridae. Characteristics of hepatitis c viral genome associated.
Characteristics of hepatitis c viral genome associated with. The boxed region represents the polyprotein coding segment. Despite the inability to culture patient viruses directly in the laboratory, efforts to define the infectious genome of hcv resulted in develop ment of experimental. Aug 17, 2005 since the discovery of the hepatitis c virus over 15 years ago, scientists have raced to develop diagnostics, study the virus and find new therapies. In the united states, more than 3 million people have chronic hcv infection. Hepatitis c virus structure national institutes of health nih. Hepatitis c virus hcv infection is a major health problem worldwide. Hepatitis c virus hcv infection is a serious global health problem that affects 180 million people worldwide and 10 million people in pakistan.
It is a spherical, enveloped, singlestranded rna virus measuring approximately 3060 nm in diameter. The hepatitis c virus particle consists of a core of genetic material rna, surrounded by an icosahedral protective shell of protein, and further covered in a lipid fatty envelope of cellular origin. Pathophysiology of hepatitis c virus infection and related. An overview of hcv molecular biology, replication and.
Current sequencing strategies require prior knowledge of the hcv genotype and subtype for efficient amplification, making it difficult to sequence samples with a rare or unknown genotype andor subtype. Wuc, zugen chend, shawna truong, gurpreet brara, shengyao sue,f,g. Hepatitis c is a flavivirus of which yellow fever is the prototype that causes nona, nonb hepatitis. The hepatitis c virus is the cause of hepatitis c and some cancers such as liver cancer hepatocellular carcinoma, abbreviated hcc and lymphomas in humans. Molecular cloning of a defective hepatitis c virus genome. Hepatitis c virus hcv is an enveloped, positivestrand rna virus classified in the hepacivirus genus within the flaviviridae family. Joy1 1british columbia centre for excellence in hivaids, vancouver, bc, canada 2british columbia centre for disease control, vancouver, bc, canada. The exact stage and mech anism by which the viral genome is released from the nucleocapsid is not currently known. Production of infectious hepatitis c virus in tissue culture. Intrahost evolutionary dynamics of the hepatitis c virus among people who inject drugs vincent montoya, anita ym howe2, weiyan dong1, winnie dong1, chanson brumme1,3, andrea olmstead1, kanna hayashi4,5, richard harrigan3, jeffrey b. Hepatitis c virus hcv is an enveloped, rna virus transmitted through bloodtoblood contact. It is estimated that three to four million people are infected with hcv every year. If untreated, 20% of patients develop liver cirrhosis, and a fraction of these progress to hepatocellular carcinoma.
Detailed analyses of hcv have been hampered by the lack of. As for other competitive pcrbased applications, this method consists of the reverse transcription and subsequent. Hcv evades innate and adaptive immunity and establishes chronic infections in 70% of cases. Hepatitis c virus hcv causes acute and chronic hepatitis which can eventually lead to permanent liver damage and hepatocellular carcinoma. Hepatitis c virus hcv infection causes chronic liver diseases and is a global public health problem. During the initial infection people often have mild or no symptoms. Genome of human hepatitis c virus hcv mary ann liebert, inc. It can ultimately result in liver cirrhosis, hepatic failure or hepatocellular carcinoma, which are responsible for hundreds of thousands of deaths each year. Since the discovery of the hepatitis c virus over 15 years ago, scientists have raced to develop diagnostics, study the virus and find new therapies. Despite the discovery of hcv over 15 years ago, our knowledge.
Molecular virology of hepatitis c virus hcv international journal. Hepatitis c virus hcv infection is the main cause of chronic hepatitis, affecting an estimated 150 million people worldwide. The nucleotide sequence of the japanese type of hepatitis c virus hcvj genome, consisting of 94 nucleotides, was determined by analyses of cdna clones from plasma specimens from japanese patients with chronic hepatitis. Subgenomic replicons of the jfh1 genotype 2a strain cloned from an individual with fulminant hepatitis replicate efficiently in cell culture. For some people, hepatitis c is a shortterm illness but for 70%85% of people who become infected with the hepatitis c.
Quantitation of hepatitis c virus genome molecules in. Once you receive a hepatitis c diagnosis, and before you start treatment, youll need another blood test to determine the genotype of the virus. Hepatitis c virus genotypes and viral concentrations in participants of a general population survey in the united states. Two viral envelope glycoproteins, e1 and e2, are surrounded in the lipid envelope. Hcv genome and life cycle hepatitis c viruses ncbi. Jun 12, 2005 hepatitis c virus hcv infection causes chronic liver diseases and is a global public health problem. Pdf infection with hepatitis c virus hcv, which is distributed worldwide, often.
Characterization of the viral genome and the structures and functions. The effects of chronic infection include cirrhosis, endstage liver disease, and hepatocellular carcinoma. Production of infectious hepatitis c virus in tissue. Molecular cloning of the human hepatitis c virus genome from.
Jake liang liver diseases section, national institute of diabetes and digestive and kidney diseases niddk, national institutes of health nih, bethesda, maryland. Hcv infec tion frequently causes chronic hepatitis, which progresses to liver. A competitive reverse transcription pcr crtpcrbased assay for the quantitative detection of hepatitis c virus hcv viremia was developed, optimized, and applied to the direct molecular analysis of clinical samples from nine patients with persistent hcv infection. The history of hepatitis c virus hcv journal of hepatology. Nov 30, 2016 electron micrograph of hepatitis c virus 19. Chronic hcv infection can progress to severe liver disease including cirrhosis and hepatocellular carcinoma.
Comparison of hcvj with the american isolate of hcv. Pdf molecular biology of hepatitis c virus researchgate. The first complete genome sequences of hepatitis c virus. Comparison of hcvj with the american isolate of hcv showed 22. Hepatitis c virus hcv is a singlestranded rna virus.
Hepatitis b virus structure, symptoms, diagnosis, treatment. Pathogenesis, natural history, treatment, and prevention of hepatitis c. Spinal cord clinical anatomy and physiology dermatomes, blood supply, shingles, lumbar puncture duration. Hepatitis b virus, a major worldwide infectious and cancer promoting agent contains a dna genome of 3226 base pairs that replicates by a reverse. The hepatitis c virus hcv attacks the liver, leading to inflammation. Hepatitis c virus an overview sciencedirect topics. Wholegenome sequencing of human pegivirus variant from an egyptian patient coinfected with hepatitis c virus. Detailed analyses of hcv have been hampered by the lack of viral culture systems. It is an enveloped, singlestranded rna virus of 5565 nm in diameter. Initial exposure to hcv is most often followed by chronic hepatitis, with only a minority of individuals spontaneously clearing the virus. Pdf the biology and pathogenesis of hepatitis viruses. Since the discovery of hcv in 1989, a large number of genetic analyses of hcv have been reported, and the viral genome structure has been elucidated. Nelson, in principles and practice of pediatric infectious diseases fifth edition, 2018. Hepatitis c virus hcv is the major etiologic agent of nona, nonb hepatitis.
Hepatitis c information division of viral hepatitis cdc. Hepatitis c virus hepatitis c virus hcv is 1 of 6 along with a, b, d, e, and g that cause viral hepatitis that was discovered in 1989 during a study to discover the cause of posttransfusion hepatitis. King md, phd, in elseviers integrated pathology, 2007. Hcvj genome contains a long open reading frame that can encode a sequence of 3010 amino acid residues. When compared with the published taiwanese hcv sequence, this defective genome. Searching for a substance with antihcv potential, we examined the effects of a variety of. Every chronic hepatitis c infection starts with an acute phase. Currently, there is no vaccine available for prevention of hcv infection due to high degree of strain variation. It infects humans only and primarily targets liver cells. Jul 07, 2014 spinal cord clinical anatomy and physiology dermatomes, blood supply, shingles, lumbar puncture duration. Hepatitis c questions and answers for health professionals. Apr 22, 2019 the hepatitis c virus is a single stranded, enveloped, positive sense rna virus. Most infections become chronic, as the body is unable to get rid of the virus.
The virus can infect the person and may cause severe inflammation of the liver leading to severe liver damage and. Acute hepatitis c usually goes undiagnosed because it rarely causes symptoms. This is the strain of the virus to which they were exposed when they were infected, often many years prior to their evaluation, and it is determined by a simple blood test. The polyprotein is processed into p1, p2, p3 regions and individual proteins by viral 3c, cellular and unknown protease activities as indicated. Subgenomic replicons of the jfh1 genotype 2a strain cloned from an individual with fulminant hepatitis replicate efficiently in. Hepatitis c virus hcv is the causative agent of hepatitis c disease in human, conclusively proved in 1989, when its genome was cloned for the first time. The virus persists in the liver in about 75% to 85% of those initially infected. Hepatitis a virus an overview sciencedirect topics. Hepatitis c virus hcv is a hepatotropic rna virus of the genus hepacivirus in the flaviviridae family, originally cloned in 1989 as the causative agent of nona, nonb hepatitis. Human pegivirus hpgv is structurally similar to hepatitis c virus hcv and was discovered 20 years ago. Molecular cloning of the human hepatitis c virus genome.
Hepatitis c virus encoded antigen recombinant c223, c200 and ns5 ortho hcv version 3. The availability of a serologic assay for hepatitis c virus in the 1980s allowed the removal of contaminated blood products from the blood supply. Hepatitis c virus structure national institutes of. Jake liang, md, liver diseases section, national institute of diabetes and digestive and kidney diseases, national institutes of health, 10 center drive, room 9b16, bethesda, md 208921800. Pairing highthroughput sequencing technologies with highthroughput mutagenesis enables genome wide investigations of pathogenic organisms. An overview of hcv molecular biology, replication and immune.
Hepatitis c virus genotypes and viral concentrations in participants of a. Whole genome sequencing of human pegivirus variant from an egyptian patient coinfected with hepatitis c virus. The results of these hemophiliacs were compared with those of previously studied hiv. It is a small 5565nmin size enveloped virus, containing positive single stranded rna of 9.
Hepatitis c virus is an rna virus that is significantly less contagious than hepatitis b virus and is usually spread through blood or blood products. Wuc, zugen chend, shawna truong, gurpreet brara, shengyao sue,f,g, yushen dua,h, vaithilingaraja arumugaswamia, c. That means the genetic code of each virus particle is contained within one continuous piece of the nucleic acid rna. Unravelling hepatitis c virus replication from genome to. Translation of the hcv genome leads to a polyprotein precursor that is co and posttranslationally processed by cellular and viral proteases to. Figure 1 hcv genome organization and processing of viral polyprotein. Its distribution, natural history and exact rule of this viral group in human hosts remain unclear.
The current treatment of care, pegylated interferon. For some people, hepatitis c is a shortterm illness but for more than 50% of people who become infected with the hepatitis c virus, it becomes a longterm, chronic infection. Hepatitis c is a liver infection caused by the hepatitis c virus hcv. Hepatitis c virus hcv is a member of the genus hepacivirus within the flaviviridae family. As a result of shared routes of transmission, coinfection with hiv is a substantial problem, and individuals infected with both viruses have poorer outcomes than do peers infected with one virus.
Genome is partially doublestranded dna that forms a covalently closed circle with 5. The functions of individual proteins are indicated. An important variable for all patients with chronic hepatitis c virus hcv is the genotype of hcv with which they are infected. The virus can infect the person and may cause severe inflammation of the. Hepatitis a virus hav is a nonenveloped rna virus and a member of the picornaviridae family. Hepatitis c virus hcv is a singlestrand rna virus that consists of approximately 9,500 nucleotides and causes chronic hepatitis. Hepatitis c virus hcv is a member of the flaviviridae family and has a singlestranded positive sense rna genome.
Hcv infection frequently causes chronic hepatitis, which progresses to liver cirrhosis and hepatocellular carcinoma. Systematic identification of antiinterferon function on. Occasionally a fever, dark urine, abdominal pain, and yellow tinged skin occurs. Investigation of the virus has been greatly hampered because it cannot be cultured in vitro. Hepatitis c questions and answers for health professionals cdc.
Hepatitis c virus encoded antigen recombinant c223, c200. Acute symptoms appear one to three months after exposure to the virus and last two weeks. This sequence codes for a polyprotein which is processed to give rise to viral proteins vp1, vp2, vp3 and others. The chimpanzee is the only experimental animal susceptible to infection with hepatitis c virus hcv. Hepatitis c virus hcv is a positive sense, singlestranded rna virus in the flaviviridae family.
Systematic identification of antiinterferon function on hepatitis c virus genome reveals p7 as an immune evasion protein hangfei qia, virginia chu b, nicholas c. Pdf cyclosporin a suppresses replication of hepatitis c. Hepatitis c is an infectious disease caused by the hepatitis c virus hcv that primarily affects the liver. Persistent infection of hepatitis c virus hcv is a major cause of liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Genotype and subtypeindependent fullgenome sequencing. Pairing highthroughput sequencing technologies with highthroughput mutagenesis enables genomewide investigations of pathogenic organisms. Hepatitis c virus hcv exhibits a high genetic diversity and is classified into 6 genotypes, which are further divided into 66 subtypes. The flaviviridae family includes yellow fever virus, west nile virus, and dengue virus. Ncr contain highly structured ires and ucrich elements respectively. A defective hepatitis c virus hcv genome in the ascitic fluid of a patient with hepatocellular car cinoma was cloned and sequenced up to the 3 polyu stretch. Four open reading frames encoding seven peptides are indicated by large arrows. The figure shows, from top to bottom, the genomes of hcv hepacivirus, pestivirus, and yellow fever virus flavivirus. Hepatitis c virus protease, helicase, and polymerase activities are also encoded in this region and are currently the focus of intense research to develop specific hepatitis c viral inhibitors. Hcv genome and life cycle hepatitis c viruses ncbi bookshelf.