RNA viruses: Hepatitis viruses

RNA Viruses: Dr. Jawad Kadhim Tarrad
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Important points about RNA viruses:
• Medically important RNA viruses comprise fourteen families.
• Most RNA viruses contain ssRNA genomes (except Reoviruses have dsRNA genome).
• RNA viruses have genome exist either single molecule(non-segmented) or multiple molecules (segmented genome as in rotavirus , influenza virus).
• All viruses contain single copy of genome (haploid) except Retroviruses have two copies of RNA(diploid).
• They replicate in cytoplasm of infected cell (except Retroviruses and Orthomyxoviruses are replicate in nucleus).
• ssRNA viruses have polarity strand, either positive strand or negative strand.
Positive strand, if the direction of nucleotide sequences arranged from 5? to 3?terminus. The genome is replicated by synthesis of negative ssRNA intermediate form, which acts as template for synthesis of positive single strand progeny genome by RNA polymerase. Also it acts as mRNA because it has same sequences of nucleotides of mRNA.
Medical positive ssRNA viruses encompass 6 families involve: Picornaviridae, Caliciviridae, Astroviridae,Togaviridae, Flaviviridae and Coronaviridae.
Negative strand, the direction of nucleotide sequences from 3? to 5? end. The genome is replicated by synthesis of positive strand intermediate form , which acts as template for synthesis of new negative single strand progeny genome .The (-)ssRNA not act as mRNA in directly, but positive ssRNA is synthesized by RNA polymerase from negative strand and it acts as mRNA.
Medical negative ssRNA viruses divided into 6 families include : Orthomyxoviridae, Paramyxoviriae, Rhabdoviridae, Filoviridae, Bunyaviridae and Arenaviridae.
• RNA viruses have nucleocapsid symmetry either icosahedral(mostly in positive strand viruses) or helical (mostly in negative strand viruses).

Hepatitis viruses:
Etiology of hepatitis in general:
• Viral hepatitis:
1. Major; they responsible for most cases of hepatitis that known as (hepatitis viruses) involve five types (A-E) at least.
2. Minor; yellow fever virus, CMV,EBV, rubella, Ebola, and others.
• Bacterial hepatitis ; Coxeilla , Leptospira.
• Protozoal hepatitis; Toxoplasma gondii.
• Fungal hepatitis; Aspergillus flavus
• Others:
1. Drug-hepatitis; analgestics(Aspirin), cardiacs(methyldopa), anesthetics (halothane), psychotropics(monoamine-oxidase inhibitors).
2. Pregnancy.
Important properties of viral hepatitis:
• Hepatitis viruses are classified into 5 types
hepatitis-A virus(HAV)
hepatitis-B virus(HBV)
hepatitis-C virus(HCV)
hepatitis-D virus(HDV)
hepatitis-E virus(HEV)
• All types of hepatitis viruses have RNA genome except type-B virus has DNA.
• All types of hepatitis viruses cause acute disease, while chronic disease caused by HBV,HCV and HDV.
• HBV,HCV and HDV infections may cause cancer in liver.
• Pathogenesis of hepatitis is mainly dependent either on immune response that causes liver damage, or on cytopathic effects.

1. Hepatitis-A virus (HAV):
• Genus : Hepatovirus.
• It has one serotype.
Important properties:
• It belongs to family picornaviridae.
• Genome is (+)ssRNA.
• Nucleocapsid is icosahedral(cubic).
• Non-enveloped (naked) virus.
Source and transmission:
• Humans are reservoir for HAV.
• It is transmitted by
1. Fecal-oral route during ingestion of fecal contaminated food and water(sea food; shellfish-oysters grown in polluted water and eaten raw).
2. It is rarely transmitted via blood because level of viremia is low and chronic infection does not occur.
Pathogenesis:
• After ingestion of HAV, it can survive in GI tract, because the virus is acid-stable (acid-resistant) and therefore, in previously HVA classified as enterovirus-72 but now been assigned its own genus hepatovirus.
• The virus probably replicates in epithelial cells of GI tract and spread to liver via blood and it cause liver damage.
• The virus is likely attack by cytotoxic T-cell that causes the damage to hepatocytes.
Diseases and C/F:
• HAV infection has short incubation period (3-6wk). HAV infection is named as infectious hepatitis.
• HAV is responsible for 60% cases of acute disease (no cause chronic , so no carriers of HAV) with sudden onset(abrupt).
• The virus release into bile duct and appears in feces roughly 2 weeks before appearance of symptoms.
• Most cases are mild or asymptomatic. Most C/F are fever , anorexia (loss of appetite), vomiting, jaundice, dark urine, and pale face.
Epidemiology:
• HAV infections are high prevalence and worldwide distribution.
• Children are most frequently infected group.
• Common-source outbreaks arise from ingestion of fecal contaminated water and food, especially sea food eg. oysters(shelfish) grown in polluted water and eaten raw.
• Usually benign infection and complete recovery spontaneously within (2-4wk) in 99% of cases and confers lifelong immunity.
Lab. Dx:
• The virus can be detected serologically in stool and in serum by ELISA for demonstration of specific antibodies (IgM, IgG) in acute phase during 2 week. If detection of anti-HAV IgM in serum of patient is positive, this result indicates acute infection with HAV, while if Anti-HAV-IgG is detected, indicate the patient is suffering from old infection (convalescence) with HAV.
• Tests for abnormal liver functions (such as bilirubin and aminotransferase ).

Prevention and treatment:
• Good hygiene and chlorination of water and sewage.
• Avoidance of contaminated food and water.
• HAV vaccine is available. It produces good level of neutralizing antibodies that persist for at least 10 year.
• No specific antiviral therapy is available.

2. Hepatitis-B virus (HBV):
• Genus: Orthohepadnavirus.
Important properties:
• It belongs to family hepadnaviridae.
• Enveloped virus.
• Capsid proteins in icosahedral.
• Genome is partially dsDNA.
• The virus is resistant to low pH.
It has three HBA antigens:
• HBsAg- is present in envelope(surface antigen).
• HBcAg-is core protein that surrounds the genome.
• HBeAg-is minor protein(enzymatic antigen).
Source and transmission:
• Humans are only natural hosts of HBV.
• Asymptomatic and chronic carriers are major source of infection.
• Three main modes of transmission :
1. Blood transfusion.
2. Sexual contact.
3. Perinatally.
Replication:
• Binding and fusing of HBV with liver cells.
• After un-coating, release of nucleic acid of virus into cytoplasm and completion of partially dsDNA. While in nucleus, synthesis of two types of strands( short and long).
• Strands of mRNA move to cytoplasm . Short strands translated into viral proteins while long strands are used as template for synthesis of ssDNA by reverse transcriptase then synthesis of dsDNA by DNA polymerase.