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Virulence Dec 2021Hepatitis A is an acute infection of the liver, which is mostly asymptomatic in children and increases the severity with age. Although in most patients the infection... (Review)
Review
Hepatitis A is an acute infection of the liver, which is mostly asymptomatic in children and increases the severity with age. Although in most patients the infection resolves completely, in a few of them it may follow a prolonged or relapsed course or even a fulminant form. The reason for these different outcomes is unknown, but it is generally accepted that host factors such as the immunological status, age and the occurrence of underlaying hepatic diseases are the main determinants of the severity. However, it cannot be ruled out that some virus traits may also contribute to the severe clinical outcomes. In this review, we will analyze which genetic determinants of the virus may determine virulence, in the context of a paradigmatic virus in terms of its genomic, molecular, replicative, and evolutionary features.
Topics: Child; Hepatitis A; Hepatitis A virus; Humans; Virulence
PubMed: 33843464
DOI: 10.1080/21505594.2021.1910442 -
Intervirology 2010Due to improved living conditions and subsequent changes in hepatitis A epidemiology, the disease burden of hepatitis A is increasing in many regions. Recently, Korea... (Review)
Review
Due to improved living conditions and subsequent changes in hepatitis A epidemiology, the disease burden of hepatitis A is increasing in many regions. Recently, Korea has faced a large, community-wide outbreak of hepatitis A, which has prompted a vaccination program. The clinical spectrum of hepatitis A virus infection ranges from asymptomatic infection to fulminant hepatitis. Clinical manifestations depend on the age of the host: less than 30% of infected young children are symptomatic, while about 80% of infected adults manifest severe hepatitis with remarkably elevated serum aminotransferases. Fulminant hepatitis is rare, with a reported incidence from 0.015 to 0.5%. Atypical manifestations include relapsing hepatitis and prolonged cholestasis, and complicated cases with acute kidney injury have been reported. Extrahepatic manifestations, such as autoimmune hemolytic anemia, aplastic anemia, pure red cell aplasia, pleural or pericardial effusion, acute reactive arthritis, acute pancreatitis, acalculous cholecystitis, mononeuritis, and Guillain-Barré syndrome, have been rarely reported. Management of hepatitis A includes general supportive care, and critical decisions regarding liver transplantation await further studies on prognostic predictors. Fundamental management of hepatitis A is active vaccination. However, a vaccination program should be adapted to the regional situation, according to differing epidemiology and disease burden.
Topics: Adult; Case Management; Hepatitis A; Hepatitis A virus; Humans; Korea; Prognosis; Young Adult
PubMed: 20068336
DOI: 10.1159/000252779 -
Cold Spring Harbor Perspectives in... Sep 2018Hepatitis A virus (HAV) is transmitted by the fecal-oral route and is a major cause of acute viral hepatitis. The clinical manifestations of HAV infection range from... (Review)
Review
Hepatitis A virus (HAV) is transmitted by the fecal-oral route and is a major cause of acute viral hepatitis. The clinical manifestations of HAV infection range from asymptomatic infection to acute liver failure (ALF), but do not include progression to chronic hepatitis. Risk factors for severe acute hepatitis A are older age (>40 years) and preexisting liver disease. Some patients may show atypical clinical features such as relapsing hepatitis, prolonged cholestasis, or extrahepatic manifestations. Almost all hepatitis A patients spontaneously recover with supportive care. However, in the case of ALF (<1%), intensive care and urgent decision on liver transplantation are required. Liver injury during hepatitis A is not directly caused by HAV but is known to be caused by immune-mediated mechanisms. In this review, the natural history and clinical manifestations of hepatitis A are described. In addition, mechanisms of immunopathogenesis in hepatitis A are discussed.
Topics: Acute Disease; Disease Progression; Hepatitis A; Hepatitis A Vaccines; Hepatitis A virus; Humans; Liver; Liver Failure, Acute; Liver Transplantation; Risk Factors
PubMed: 29440324
DOI: 10.1101/cshperspect.a031708 -
Viruses Sep 2021The hepatitis A virus (HAV) is a leading cause of acute viral hepatitis worldwide. It is transmitted mainly by direct contact with patients who have been infected or by... (Review)
Review
The hepatitis A virus (HAV) is a leading cause of acute viral hepatitis worldwide. It is transmitted mainly by direct contact with patients who have been infected or by ingesting contaminated water or food. The virus is endemic in low-income countries where sanitary and sociodemographic conditions are poor. Paradoxically, improving sanitary conditions in these countries, which reduces the incidence of HAV infections, can lead to more severe disease in susceptible adults. The populations of developed countries are highly susceptible to HAV, and large outbreaks can occur when the virus is spread by globalization and by increased travel and movement of foodstuffs. Most of these outbreaks occur among high-risk groups: travellers, men who have sex with men, people who use substances, and people facing homelessness. Hepatitis A infections can be prevented by vaccination; safe and effective vaccines have been available for decades. Several countries have successfully introduced universal mass vaccination for children, but high-risk groups in high-income countries remain insufficiently protected. The development of HAV antivirals may be important to control HAV outbreaks in developed countries where a universal vaccination programme is not recommended.
Topics: Antiviral Agents; Disease Outbreaks; Hepatitis A; Hepatitis A virus; Homosexuality, Male; Humans; Incidence; Male; Risk Factors; Sexual and Gender Minorities; Travel
PubMed: 34696330
DOI: 10.3390/v13101900 -
International Journal of Molecular... Jun 2022Hepatitis A virus (HAV) infection is a major cause of acute viral hepatitis globally, which can occasionally lead to acute liver failure (ALF) and acute-on-chronic liver...
Hepatitis A virus (HAV) infection is a major cause of acute viral hepatitis globally, which can occasionally lead to acute liver failure (ALF) and acute-on-chronic liver failure (ACLF), which often result in death without liver transplantation [...].
Topics: Acute-On-Chronic Liver Failure; Hepatitis A; Hepatitis A virus; Hepatitis, Viral, Human; Humans; Liver Transplantation
PubMed: 35806219
DOI: 10.3390/ijms23137214 -
Clinical Microbiology Reviews Jan 2006Current serologic tests provide the foundation for diagnosis of hepatitis A and hepatitis A virus (HAV) infection. Recent advances in methods to identify and... (Review)
Review
Current serologic tests provide the foundation for diagnosis of hepatitis A and hepatitis A virus (HAV) infection. Recent advances in methods to identify and characterize nucleic acid markers of viral infections have provided the foundation for the field of molecular epidemiology and increased our knowledge of the molecular biology and epidemiology of HAV. Although HAV is primarily shed in feces, there is a strong viremic phase during infection which has allowed easy access to virus isolates and the use of molecular markers to determine their genetic relatedness. Molecular epidemiologic studies have provided new information on the types and extent of HAV infection and transmission in the United States. In addition, these new diagnostic methods have provided tools for the rapid detection of food-borne HAV transmission and identification of the potential source of the food contamination.
Topics: Animals; Hepatitis A; Hepatitis A virus; Humans; Molecular Epidemiology
PubMed: 16418523
DOI: 10.1128/CMR.19.1.63-79.2006 -
Viruses May 2021Hepatitis A virus (HAV) infection is a common cause of acute viral hepatitis worldwide. Despite decades of research, the pathogenic mechanisms of hepatitis A remain... (Review)
Review
Hepatitis A virus (HAV) infection is a common cause of acute viral hepatitis worldwide. Despite decades of research, the pathogenic mechanisms of hepatitis A remain incompletely understood. As the replication of HAV is noncytopathic in vitro, a widely accepted concept has been that virus-specific cytotoxic T cells are responsible for liver injury. However, accumulating evidence suggests that natural killer (NK) cells, NKT cells, and even non-HAV-specific CD8 T cells contribute to liver damage during HAV infection. In addition, intrinsic death of virus-infected hepatocytes has been implicated as a cause of liver injury in a murine model of hepatitis A. Furthermore, genetic variations in host factors such as T cell immunoglobulin-1 (TIM1) and IL-18 binding protein (IL-18BP) have been linked to hepatitis A severity. This review summarizes the current knowledge of the mechanisms of hepatocellular injury in hepatitis A. Different mechanisms may be involved under different conditions and they are not necessarily mutually exclusive. A better understanding of these mechanisms would aid in diagnosis and treatment of diseases associated with HAV infection.
Topics: Animals; Carcinoma, Hepatocellular; Hepatitis A; Hepatitis A virus; Hepatocytes; Humans; Liver; Liver Neoplasms; Mice
PubMed: 34066709
DOI: 10.3390/v13050861 -
MBio Apr 2023Viruses lack the properties to replicate independently due to the limited resources encoded in their genome; therefore, they hijack the host cell machinery to replicate... (Review)
Review
Viruses lack the properties to replicate independently due to the limited resources encoded in their genome; therefore, they hijack the host cell machinery to replicate and survive. Picornaviruses get the prerequisite for effective protein synthesis through specific sequences known as internal ribosome entry sites (IRESs). In the past 2 decades, significant progress has been made in identifying different types of IRESs in picornaviruses. This review will discuss the past and current findings related to the five different types of IRESs and various internal ribosome entry site -acting factors (ITAFs) that either promote or suppress picornavirus translation and replication. Some IRESs are inefficient and thus require ITAFs. To achieve their full efficiency, they recruit various ITAFs, which enable them to translate more effectively and efficiently, except type IV IRES, which does not require any ITAFs. Although there are two kinds of ITAFs, one promotes viral IRES-dependent translation, and the second type restricts. Picornaviruses IRESs are classified into five types based on their use of sequence, ITAFs, and initiation factors. Some ITAFs regulate IRES activity by localizing to the viral replication factories in the cytoplasm. Also, some drugs, chemicals, and herbal extracts also regulate viral IRES-dependent translation and replication. Altogether, this review will elaborate on our understanding of the past and recent advancements in the IRES-dependent translation and replication of picornaviruses. The family is divided into 68 genera and 158 species. The viruses belonging to this family range from public health importance, such as poliovirus, enterovirus A71, and hepatitis A virus, to animal viruses of great economic importance, such as foot-and-mouth disease virus. The genomes of picornaviruses contain 5' untranslated regions (5' UTRs), which possess crucial and highly structured stem-loops known as IRESs. IRES assemble the ribosomes and facilitate the cap-independent translation. Virus-host interaction is a hot spot for researchers, which warrants deep insight into understanding viral pathogenesis better and discovering new tools and ways for viral restriction to improve human and animal health. The cap-independent translation in the majority of picornaviruses is modulated by ITAFs, which bind to various IRES regions to initiate the translation. The discoveries of ITAFs substantially contributed to understanding viral replication behavior and enhanced our knowledge about virus-host interaction more effectively than ever before. This review discussed the various types of IRESs found in , past and present discoveries regarding ITAFs, and their mechanism of action. The herbal extracts, drugs, and chemicals, which indicated their importance in controlling viruses, were also summarized. In addition, we discussed the movement of ITAFs from the nucleus to viral replication factories. We believe this review will stimulate researchers to search for more novel ITAFs, drugs, herbal extracts, and chemicals, enhancing the understanding of virus-host interaction.
Topics: Animals; Humans; Picornaviridae; Internal Ribosome Entry Sites; Foot-and-Mouth Disease Virus; Ribosomes; Hepatitis A virus; Protein Biosynthesis; RNA, Viral
PubMed: 36939331
DOI: 10.1128/mbio.00358-23 -
Cold Spring Harbor Perspectives in... Dec 2018Hepatitis A virus (HAV) is a positive-strand RNA virus classified in the genus of the family It is an ancient virus with a long evolutionary history and multiple... (Review)
Review
Hepatitis A virus (HAV) is a positive-strand RNA virus classified in the genus of the family It is an ancient virus with a long evolutionary history and multiple features of its capsid structure, genome organization, and replication cycle that distinguish it from other mammalian picornaviruses. HAV proteins are produced by cap-independent translation of a single, long open reading frame under direction of an inefficient, upstream internal ribosome entry site (IRES). Genome replication occurs slowly and is noncytopathic, with transcription likely primed by a uridylated protein primer as in other picornaviruses. Newly produced quasi-enveloped virions (eHAV) are released from cells in a nonlytic fashion in a unique process mediated by interactions of capsid proteins with components of the host cell endosomal sorting complexes required for transport (ESCRT) system.
Topics: Animals; Capsid Proteins; Endosomal Sorting Complexes Required for Transport; Genome, Viral; Hepatitis A Virus, Human; Hepatitis A virus; Humans; Virion; Virus Replication
PubMed: 29610147
DOI: 10.1101/cshperspect.a033480 -
Nature Jan 2015Hepatitis A virus (HAV) remains enigmatic, despite 1.4 million cases worldwide annually. It differs radically from other picornaviruses, existing in an enveloped form...
Hepatitis A virus (HAV) remains enigmatic, despite 1.4 million cases worldwide annually. It differs radically from other picornaviruses, existing in an enveloped form and being unusually stable, both genetically and physically, but has proved difficult to study. Here we report high-resolution X-ray structures for the mature virus and the empty particle. The structures of the two particles are indistinguishable, apart from some disorder on the inside of the empty particle. The full virus contains the small viral protein VP4, whereas the empty particle harbours only the uncleaved precursor, VP0. The smooth particle surface is devoid of depressions that might correspond to receptor-binding sites. Peptide scanning data extend the previously reported VP3 antigenic site, while structure-based predictions suggest further epitopes. HAV contains no pocket factor and can withstand remarkably high temperature and low pH, and empty particles are even more robust than full particles. The virus probably uncoats via a novel mechanism, being assembled differently to other picornaviruses. It utilizes a VP2 'domain swap' characteristic of insect picorna-like viruses, and structure-based phylogenetic analysis places HAV between typical picornaviruses and the insect viruses. The enigmatic properties of HAV may reflect its position as a link between 'modern' picornaviruses and the more 'primitive' precursor insect viruses; for instance, HAV retains the ability to move from cell-to-cell by transcytosis.
Topics: Animals; Capsid; Capsid Proteins; Crystallography, X-Ray; Evolution, Molecular; Hepatitis A virus; Hot Temperature; Humans; Hydrogen-Ion Concentration; Insecta; Models, Molecular; Phylogeny; Picornaviridae; Transcytosis; Virion; Virus Internalization
PubMed: 25327248
DOI: 10.1038/nature13806