The 5 Hepatitis Viruses at a Glance, A,B,C,D & E
Part I. For the novel reader
The Liver at a glance
Each year, liver inflammation kills over 1.4 million people worldwide. Hepatitis causes permanent liver inflammation and leads to hepatocellular carcinoma (HCC). In the healthy liver, inflammatory processes are intentionally stimulating growth and repair thus restoring normal liver ‘architecture’. Liver inflammation is a delicate balance of damage vs. regeneration. If the inflammation in the liver is excessive it will lead to scar tissue (fibrosis). Hepatic viruses does not actually kill the cells it infects, however, it triggers an inflammatory immune response (Hepatitis). This immune response quickly clears the infection and destroys the liver in a slow manner, thus causing HCC. Many years of fibrosis build up will lead to cirrhosis, (abnormal liver architecture and function) and reduces the mechanical / chemical function of the liver. The tumors made by chronic cirrhosis is difficult to find, and diagnose. HCC is the 5th most common cancer in the world, with an estimated 800,000 new diagnoses every year Researchers are not exactly sure why some people can get cirrhosis of the liver from hepatitis when some others can have chronic hepatitis (C) infections that cause very little harm to their livers. Many factors have been theorized including genetics, alcohol consumption evolutionary components of race and age.
Hepatitis Types at a glance
Hepatitis A is an acute, but benign form of viral hepatitis. Hep A is the least threatening virus of all the hepatitis types and is self limiting in nature. Acute hepatitis B can range from sub-clinical disease to a full blown hepatic failure. Patients with chronic hepatitis B are at more risk for developing HCC, or formally known as hepato-cellular carcinoma, and people of Asian decent seem to be more at risk for Hep B than the rest of the population. Hepatitis C has only been a recent find, however, a permissive cell culture system for propagating HCV hasn’t been established. This has lead to the production of specific drugs against HCV, however, the correct diagnosis is critical in treatment. The HDV infection occurs simultaneously with the hepatitis B infection. Hep D is a co-infector or super-infector of hepatitis type B). Hepatitis E virus is (ET-NANBH) and is clinically indistinguishable from hepatitis A. Hep A is a mild infection with virtually no effects of normal living, with the only exception that it affects some pregnant women. Pregnant women seem to be more susceptible to severe diseases and excessive mortality while infected with Hepatitis type E. Side note: The HGV/GBV-C has been classified as a flavivirus and can cause chronic acute hepatitis.
Genotyping (All Hepatitis Viruses A, B, C, D, E,)
Table found on wikipedia with the genome types of all 5 hepatitis viruses:
| HAV | HEV | HBV | HCV | HDV | |
| Transmission | Enteric | Enteric | Parenteral | Parenteral | Parenteral |
| Classification | Picornavirus | Hepevirus | Hepadnavirus | Hepacivirus | Deltavirus |
| Genome | +ssRNA | +ssRNA | +dsDNA | +ssRNA | -ssRNA |
| Incubation period | 15–45 days | 15–60 days | 45–160 days | 15–150 days | 30–60 days |
| Chronicity | No | No | Yes (uncommon) | Yes (common) | Yes – with hepatitis B |
Comparisons of Hepatitis Types
Similarities
Differences
http://www.cdc.gov/hepatitis/C/cFAQ.htm
http://www.immunize.org/catg.d/p4075abc.pdf
General Genetics
Life Cycle of HCV
The complete life cycle of HCV happens in the cytoplasm of the host cell and the viral RNA does not have to enter the nucleus of the cell. The cellular and viral proteins both play a role in the replication of HCV.
The binding of HCV into the host cell begins with receptor-mediated endocytosis (RME), by means of a ligand bound surface receptor on the host cell. Viral tropism is a major problem with HCV, and we do not understand or pinpoint a single direct ligand for the glycoprotein receptor process. Some models suggest that there is a LDL (Low-Density Lipoprotein) and the LDLR (LDL Receptor) associated with the virus receptor binding. Still, other models suggest that there are GAGs (Glycosaminoglycans) signaling the receptors for HCV. When the virus HCV is uncoated it releases its +RNA genome onto the host’s cytoplasm where it takes advantage of the host cell’s ribosomes, where it then translates into viral proteins, which consist of 10 HCV structural and other essential proteins.
HCV’s structural proteins are: capsid protein C, E1, E2 and p7. HCV’s non structural proteins are: NS2, NS3, NS4A, NS4B, NS5A and NS5B.
Both the viral and cellular proteases catalyze reactions and separate the genome into their respectful proteins. Some of the regulating enzymes are auto-catalytic in nature (zinc) and produce the non-structural proteins such as E1 and E2. The NS5B protein is the RNA-dependent RNA polymerase that catalyzes the replication of HCV RNA, and was discovered through therapeutic clinical trials.
Replicase is then assembled at the endoplasmic reticulum membrane. Replicase plays a part in the synthesis of the intermediate (-) strand RNA and is used as a template for the production of (+) strand RNAs. It is this new (+) sense RNA that forms the genome of the new HepC virion and is encapsulated with HCV structural proteins and makes up the ‘nucleocapsid’. In the lumen of the ER the nucleocapsid is enveloped by budding (through the membrane). At this point the virions are infectious and transported through the Golgi and then to the plasma membrane of the host cell, and then released into the organism’s blood route.
HCV is error prone because its RdRp has no proofreading mechanism to correct errors during strand synthesis, thus mutations occur frequently.
HCV has 2 primary ways that it can evade the human immune system. 1) HCV inhibits the Interferon regulatory factors-3 signaling mechanism. Thus, by blocking the IRF3, the immune response is stopped.
Another method, 2) HCV’s mutations play a role in the inactivation of B and T cell epitopes. These T cell epitopes are located all over the viral poly-protein, and more often than not, are inhibit binding to MHC (Major Histocompatibility Complex) molecules. IFN-Alpha (Interferon-Alpha) is usually the common treatment for HCV. IFN (pegylated interferons and ribavirin, together) acts indirectly by binding to specific cellular receptors, which in turn induce an intra-cellular antiviral response.
HCV: https://www.qiagen.com/geneglobe/pathwayview.aspx?pathwayID=218
Life cycle of HBV:
HBV from web site: https://www.qiagen.com/geneglobe/pathwayview.aspx?pathwayID=217
Simplified Pathway for Hepatitis C
Detailed Pathways and Signaling for Hepatitis C:
Images and description by National Center for Biotechnology Information of the life cycle of the hepatitis C virus. Found on Web from: http://www.ncbi.nlm.nih.gov
Diagnosis
Symptoms will usually show up 2 – 6 weeks after being exposed to the hepatitis A virus. They are usually mild, but may last for up to several months, especially in adults.
Signs
- Enlarged and tender liver.
- Blood tests may show:
- Raised IgM and IgG antibodies to hepatitis A (IgM is usually positive before IgG)
- Elevated liver enzymes (liver function tests), especially transaminase enzyme levels
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001323/
Transmission
- Hepatitis A and E are transmitted by the enteric, that is digestive or by fecal routes.
- Hepatitis B can be transmitted through blood, sweat, tears, saliva, semen, vaginal secretions, and breast milk.
- Hepatitis C is transmitted primarily blood to blood contact
- Hepatitis D is transmitted in the same way as hepatitis B. Hepatitis D can only exist with the hepatitis B virus
- Transmission is also a major concern with transplants of organs from patient to patient.
(http://menshealth.about.com/cs/diseases/a/hepatitis_4.htm)
Treatments
- Hepatitis A: No specific treatment exists. Your body will clear the hepatitis A virus on its own. Hepatitis A treatment usually focuses on coping with signs and symptoms of hepatitis A infection.
- Hepatitis B: Receiving an injection of hepatitis B immune globulin within 24 hours of coming in contact with the virus may protect from developing hepatitis B. Antiviral medications help fight the virus and slow its ability to damage your liver. If your liver has been severely damaged, a liver transplant may be an option.
- Hepatitis C: Hepatitis C infection can be treated with antiviral medications.
- Hepatitis D: Treatment for acute hepatitis D is focused on dealing with any symptoms or complications that may occur. Most people recover completely within a few months.
- Hepatitis E: Treatment for acute hepatitis E is also focused on dealing with any symptoms or complications that may occur. Most people recover completely within a few months as well.
(www.mayoclinic.com)
(emedicine.medscape.com)
Vaccines
Vaccinations and future edible vaccinations through genetically altered pharmacogenomics, and plants.
In 1997 the first human clinical trial for a edible vaccine where the volunteers ate raw potatoes that were genetically altered for combating diarrhea causing E. coli. The results were that 10 / 11 of volunteers had 4 times the rises in serum antibodies.
Trials
a. Harvard Medical School, in alliance with Massachusetts General Hospital, starts 7 trials for Hepatitis C research. March 19th 2010: A Pilot Study of the Grapefruit Flavonoid Naringenin for HCV Infection – nutritional approaches for Hepatitis C.
http://www.harvardtrials.org/topics/6526
b. A Study of Response-Guided Duration of Combination Therapy With GS-9190, GS-9256, Pegasys® and Copegus® in Previously Untreated Subjects With Genotype 1 Chronic Hepatitis C.
http://clinicaltrials.gov/ct2/show/NCT01225380
News
On Wednesday, March 18, 2009, researchers at Harvard University found a new way to block reproduction of the hepatitis C virus by targeting not the virus itself but the human genes the virus uses to replicate itself in the Hepatitis C life cycle.
http://news.harvard.edu/gazette/?s=hepatitis&sort_by=date
Tareq Yasin, Thomas R Riley, Ian R Schreibman, Current treatment of choice for chronic hepatitis C infection; Infection and Drug Resistance, January 11th, 2011:4 Pages 11 – 18 DOI 10.2147/IDR.S4827
Al Olaby, Reem R (2011). “Hepatitis C virus RNA assays: current and emerging technologies and their clinical applications”. Expert review of molecular diagnostics (1473-7159), 11 (1), p. 53. DOI: 10.1586/erm.10.101
Ferguson, McKenzie C (2011). “Current Therapies for Chronic Hepatitis C”. Pharmacotherapy (0277-0008), 31 (1), p. 92. DOI: 10.1592/phco.31.1.92
Zhao S, Tang L, Fan X, Chen L, Zhou R, Dai X. Comparison of the efficacy of lamivudine and telbivudine in the treatment of chronic hepatitis B: a systematic review. Virol J. 2010;7:211.
Videos
Hepatitis A
Funny rap song – hardly science, but socially educational. 1.5 minutes run time.
http://www.youtube.com/watch?v=Te-rDGG4azc&feature=related
Hepatitis B and C
Overview of immune response of Hep B and C. Made by ViRexx Medical Corp, a small cap CDN biotech company. 4 minutes run time.
Programmed and activated T and B cells. Key words: T-cells, antigens, killer cells.
http://www.youtube.com/watch?v=Il-APEVm-YY&feature=related
Hepatitis C
Covers the basic Liver location and function, and basic Hepatitis C pathway. 1.4 minutes run time.
http://www.youtube.com/watch?v=y6osMO5xnag
Hepatitis D
Vertex Pharmaceuticals unveiled more positive results on the drug its developing with Johnson & Johnson to treat Hepatitis C. and covers Type D also. 4 min run time.
http://video.cnbc.com/gallery/?video=1316903513
Hepatitis E
Hepatitis G
Academia and Research Links
From this site you can easily access detailed information regarding any virusfamily, including basic and detailed links to each of the 5 Hepa viruses we covered.
http://www.microbiologybytes.com/virology/
From this site you can easily access other related retro virus information and video, academia and journals by Hepatitis (and other viral) categories.
http://www.virology.wisc.edu/virusworld/viruslist.php?virus=hev
Biotechnology
Questions about the Future and Biotechnology
Who is to say what the status of infectious disease will be in the late 21st century? Modern medicine is only 100 years old, at best, including such pioneers as James Watson, Francis Crick and Maurice Wilkins with their discovery (proof of latching) of DNA . Modern medicine (now known as genetics) is competing with millions (and perhaps billions) of years of biological evolution – especially concerning viruses, which may be the source of all biological life anyway. Vaccines, antibiotics, and antiviral drugs are common place household terms today. Researchers are asking themselves if resistant strains of disease can overpower their ability to develop new drugs and vaccines.
Virus vectors and gene therapy
Part II. For the Detailed Researcher
Hepatitis A in Detail
For detailed information on Hepatitis A GO TO:
http://www.microbiologybytes.com/virology/HAV.html
Hepatitis B in Detail
Hepatitis B is the single most responsible factor in liver cancer worldwide.
Asian and Pacific Islanders are more susceptible to Hepatitis B.
Even though a small portion of the population (0.2-0.5% of the U.S. population) has chronic hepatitis B infection, this includes approximately 1.25 million people. Of these, ½ are Asian and Pacific Islander (API) Americans. 5-15% of API immigrants have chronic hepatitis B. In some Pacific Rim countries as many as 10-20% of the population are chronically infected with Hepatitis B.
Above found on Web at: http://liver.stanford.edu/Education/faq.html
HBV – quick facts:
- HBV is a global epidemic that has infected 370 million people. HBV is responsible for nearly 1 million deaths annually. Even though there is a vaccine for Hepatitis B Virus (HBV) an infection kills one person every 30-45 seconds.
- Nearly 2/3 of the infected population are unaware of their infection, and in turn leads to HBV becoming one of the largest health threats in the world.
- When compared to HIV, HBV is nearly ten times more prevalent in the world. When comparing continents, HIV is more prevalent in Africa whereas HPV is more prevalent in Asia.
- Hepatitis B Virus is approximately 100 times more infectious than HIV.
- Hepatitis is very similar to HBV which infects about 180 million people worldwide. There is no cure for HCV and there is no vaccine that has been developed to date.6. HBV and Hepatitis C together have infected 530 million of the 6 billion people worldwide.7. The HBV in pregnant women who are carriers of hepatitis B virus can pass this infection to their babies during childbirth.
- HBV and Hepatitis C together have infected 530 million of the 6 billion people worldwide.
- The HBV in pregnant women who are carriers of hepatitis B virus can pass this infection to their babies during childbirth.
- The most common types of people who are at the highest risk for HBV include illegal intravenous drug users, haemophiliacs, homosexual and bisexual males, sexually active heterosexual persons with multiple partners, prisoners, patients on haemodialysis, health care staff who have sustained a needle stick injury and also include people who have body piercings and tattoos. Other world populations have a higher incidence and include Alaskan Eskimos, Pacific Islanders, Haitian and Indo-chinese immigrants.
- Hepatitis B recombinant vaccine is a very safe vaccine as it has no human blood or blood products and it is produced by genetic re-engineering process and usually requires three injections for protection over a six months period.
Above found on web at: http://www.who.int/csr/resources/publications
Hepatitis B Particles
Hepatitis C in Detail
Hepatitis-C Virus (HCV) belongs to the Flaviviridae family. Acute infection occurs in only a few patients. In most cases the virus results in chronic infection taking 10-20 years before the emergence of liver disease, which is often accompanied by only mild or vague symptoms.
For detailed information on Hepatitis C GO TO:
http://www.microbiologybytes.com/virology/HCV.html
Hepatitis D in Detail
Peginterferon plus Adefovir versus Either Drug Alone for Hepatitis Delta; Wedemeyer H., Yurdaydìn C., Dalekos G.N., et al. Peginterferon plus Adefovir versus Either Drug Alone for Hepatitis Delta; N Engl J Med 2011; 364:322 – 331, published on January 27, 2011. Found on web at: http://www.nejm.org/search?q=hepatitis+delta&asug=hepatitis+D
For detailed information on Hepatitis C GO TO:
http://www.microbiologybytes.com/virology/HDV.html
Hepatitis E in Detail
The U.S. Centers for Disease Control and Prevention (CDC) claim that a new experimental vaccine to fight hepatitis E has made its way and that it has the potential to eradicate the disease, in January 2011.
Above found on web at: http://topnews.us/content/224720-chinese-study-finds-vaccine-hepatitis-e-experts-feel-vaccine-has-potential-annihilate
For detailed information on Hepatitis E GO TO:
http://www.microbiologybytes.com/virology/HEV.html
Hepatitis G in Detail
Non-A, non-B hepatitis viruses
These viruses are serologically distinct from HAV and HBV. They have not been fully characterized, and their mode of replication and antigenic composition remain unclear.
Detailed Genetics
Hepatitis C virus controls interferon production through PKR activation.
From web http://www.microbiologybytes.com/virology/HCV.html
Ribavirin is a drug that is used against HCV, HSV, measles, mumps, Lassa fever. Its chemical type is Triazole carboxamide and it targets the RNA mutagen.
For detailed information on Viral Hepatitis Genetics GO TO:
http://www.microbiologybytes.com/virology/Genetics.html
The 5 Hepatitis Viruses A, B, C, D and E 