Virology (Hepatitis virus)

# Virology (Hepatitis virus) ###### tags: `共筆` ## Hepatitis viruses * **Hepatocyte-tropic**, cause liver diseases > Other viruses such as ++yellow fever virus++, ++cytomegalovirus (CMV)++, ++herpes simplex virus (HSV)++, ++enteroviruses++ and ++rubella++ virus also infect hepatocytes * Hepatitis viruses cause icteric(黃疸) symptoms of jaundice (黃疸) * Release of liver enzymes. * ALT: alanine aminotransferase (**GPT**) * AST: aspartate aminotransferas (**GOT**) * ALP: alkaline phosphatase --- ![](https://i.imgur.com/MAMToVV.png) --- ### Hepatitis virus A * [Picornavirus](#Picornavirus) (+ssRNA, naked icosahedral capsid) * **Non-cytolytic** * Spread by the **fecal-oral route** * ++Does not cause chronic liver disease++, rarely fatal * **One serotype** of HAV > 抗體可有效阻擋再次感染 #### Pathogenesis and epidemiology * Oropharynx -> intestine -> blood -> liver (replicate in hepatocytes and **Kupffer cells**(庫佛氏細胞)) -> release into the bile -> stool * ++Liver damage and clinical syndrome++ result of **immune response** * **Raw or improperly treated sewage** can taint the water supply and **contaminate shellfish**. * **Resistant to temperature** (60° C), **stable at pH 1** #### Clinical Features * Discrete(離散) onset of symptoms(ex: 疲倦、腹痛、沒食慾、噁心、嘔吐) * **Jaundice** or elevated serum ATL/AST levels, dark urine, light stool * ++Adults usually more symptomatic++ > 小孩因為免疫反應比較弱，臨床症狀會比較輕微 * Most cases resolve spontaneously in 2-4 weeks. * **Fulminant hepatitis** (猛爆性肝炎) 1-3 people per thousand HAV infections: **> 50% mortality** rate with medical intervention. #### Treatment * **Supportive**- no specific role of antiviral therapy * **Lifelong immunity** #### Prevention * Hygiene (e.g., hand washing) * Sanitation (e.g., clean water sources) * Hepatitis A vaccine (pre-exposure) * Immune globulin (pre- and post-exposure) --- ### Hepatitis B virus * **Hepadnavius** * Enveloped, **partial dsDNA** (++longer -DNA strand than the +DNA strand++) * Limited tissue tropisms and host range. #### Structure * 42nm enveloped virus -> Dane particles (Partial dsDNA genome (3.2kb)) * 22nm spheres and filaments -> Decoy particles (誘餌) (not infectious, no DNA) > divert the immune system by binding Ab and complement #### Life cycle ##### Viral genome * Relax circular (RC)-DNA > (-) strand: full length > (+) strand: < full length * P (polymerase) is linked to the**5’ end of the (-)strand DNA** * pgRNA (pregenomic): terminal redundant (**for DNA replication**) ##### Transcription * Four promoters, 5 transcripts (by **Leaky scanning**) ##### Replication cycle 1. **Repair** of the gapped + DNA strand => CCC DNA(Covalently closed circular (**mini chromosome**)) (into **nucleus**) 2. P protein (**RTase activity**) and capsid are translated from pregenome transcript 3. P protein binds to pregenome at 3’ (**RNA-P complex**), packaged, and **makes -DNA in the core** (**RTase activity**) 4. Making the +DNA strand (**DNA polymerase activity**) by P protein in the core after **digesting the RNA away** (**RNase H activity**) 5. Encapsidation -> Viral **maturation completed on ER** 6. Released by **exocytosis** ![](https://i.imgur.com/4438FtT.png =500x) #### Retrovirus v.s. Hepadnavirus ![](https://i.imgur.com/YnPEiF1.png =500x) #### HBV Pathogenesis * Immune response (cytotoxic T cell) to viral antigens expressed on hepatocyte cell surface responsible for clinical syndrome. * Acute hepatitis * Fulminant hepatitis(猛爆性肝炎) * Chronichepatitis * Asymptomatic carrier * Chronic-persistent hepatitis * Chronic active hepatitis * Complications: * Primary hepatocellular carcinoma(原發性肝細胞癌) * Cirrhosis(肝硬化) #### Transmission * **Sexual, parenteral(胃腸外的), and perinatal(圍產期)** * Vertical transmission > 並非藉由胎盤傳染，而是在生產過程中感染 #### Serology * HbsAg = Disease * Anti-HbsAg = **Vaccined / Cure** * IgM anti-HBcAg = New infection * IgG anti-HBcAg = Old infection * HBeAg = High infectivity * Anti-HBeAg = Low infectivity > The **detection of HBeAg** is the best correlate to the presence of infectious virus. #### Treatment * Antiviral medications: Anti-polymerase, Anti-RT * Interferon injections #### Prevention * ==**Recombinant subunit vaccines (against HBsAg)**== --- ### Hepatitis C virus * A member of Flaviviridae (but not an arbovirus) * + RNA genome, enveloped * **Blood-borne pathogen** that infects ++hepatocytes++ * High mutation, no vaccines #### Replication * 5’-IRES: 5'-cap * Polyprotein #### Clinical Features * Acute infection * **Asymptomatic** * -> Chronic hepatitis * **Cirrhosis(肝硬化)** * **Hepatocellular carcinoma(原發性肝細胞癌)** #### Pathogenesis * Clinical illness due more to immune response #### Therapy * Effective antivirals are available * Interferon alpha and Ribavirin > Systemic side effects (fatigue, myalgia, depression, anemia to name a few). --- ### Hepatitis D virus * Defective virus that requires **co-infection with hepatitis B** for replication. * Enveloped (**from HBV**) with (-)ssRNA circular genome. * A nucleus virus * **Delta antigen** (large and small) #### Structure * Genome surrounded by delta antigen * Core is surrounded by an **HbsAg-containing coat**. * Viral RNA is folded into a **rod-like structure** (=>單股DNA互補) #### Life cycle * **Rolling-circle replication mechanism** ![](https://i.imgur.com/AyU97ns.png =400x) * RNA editing * dsRNA adenosine deaminase > A -> I => UAG(Stop) -> UGG(Trp) ![](https://i.imgur.com/zQRKncc.png =400x) #### Pathogenesis * Damage to the liver occurs as a result of the **direct cytopathic effect of the delta agent** * Co-infection(共同感染): infection with B at the same time * Superinfection(重複感染): acquisition of Hep D in **chronically** Hep B * Causes **fulminant hepatis**(猛爆性肝炎) * **控制HBV感染**為目前唯一避免HDV感染的辦法 --- ### Hepatitis E virus * **Hepeviridae** (肝炎病毒科) * A small, round-structured +ssRNA virus, **naked**, icosahedral particle * **Acute**, **self-limiting infection**; high mortality in pregnant women #### Epidemiologic Features * Fecal-oral route transmission (Contaminated drinking water.) * Only causes **acute disease** * ++Minimal person-to-person transmission++ * **地方性傳染病**