Hepatitis B and Hepatitis D virus
AssessmentsHepatitis B and Hepatitis D virus
USMLE® Step 1 style questions USMLE
A virologist is evaluating the genetics of certain viruses. In one study on two distinct viruses, virus A and virus B, the virologist notices that virus A only causes infection in the presence of virus B, as the genetic material of virus B produces protein that serves both virus A and B. He also notes that in the absence of virus B, virus A cannot complete its structure and propagate. Virus A most likely resembles which of the following viruses?
Hepatitis B and Hepatitis D virus exam links
Content Reviewers:Viviana Popa, MD, Rishi Desai, MD, MPH
Contributors:Kaia Chessen, MScBMC, Tanner Marshall, MS, Sam Gillespie, BSc, Stefan Stoisavljevic, MD
Hepatitis B virus, or Hep B virus for short, is a member of the hepadnavirus family; hepatitis D virus, or Hep D virus, is a deltavirus. They both cause hepatitis, or inflammation of the liver. Even though they both cause hepatitis, hepatitis D virus cannot cause the disease by itself, and needs hepatitis B virus to replicate.
Both hep B and D viruses are enveloped, so they’re surrounded by a membrane. To make things interesting, the membrane of both viruses contains hepatitis B viral proteins - specifically, they both have a surface antigen called HBs. Beneath the membrane there is a protein shell called a capsid, which has more antigens. HB core, or HBc, is in the capsid of hepatitis B. There is also an HB envelope or HBe antigen for short, which is a variant of HBc but it’s not really part of the virus. It’s secreted, and can be found in infected individuals' serum. Delta antigen or HDAg for short is in the capsid of hepatitis D virus.
Inside the capsid, there’s the viral genetic material. Now, hep B is a DNA virus, which means that its capsid contains partial double-stranded circular DNA, which is made of a long and short strand, so there is a part where the long strand is single stranded. And it also has DNA polymerase, which is an enzyme with DNA- and RNA-dependent activity, meaning it can convert DNA to RNA and vice versa. On the other hand, hep D is an RNA virus, so its capsid contains single-stranded circular RNA in a rod-like folded structure, which is why host cell enzymes can use it as double-stranded DNA.
The main source of hepatitis B virus is blood, but it can also be found in other bodily fluids like milk, amniotic fluid, vaginal secretions and semen. So, routes of transmission include: sexual contact; contaminated blood, either following transfusions or injections with contaminated needles, the latter being more common in people who use intravenous drugs. The virus can also be passed from an infected mother to the baby during childbirth. Rarely, during the pregnancy the virus can pass through the placental barrier, which is a kind of a very thin wall that brings the mother’s and fetus' blood very close, and allows them to exchange some substances like oxygen, IgG antibodies, waste products and unfortunately certain microbes. More commonly the virus can pass from an infected individual to the child during birth because of the close contact between the individual's blood and secretions with the child. It is still not certain if C section can protect against this kind of transmission. Hepatitis D virus spreads the same way, but it only causes disease in individuals with an active hepatitis B infection.
Alright, now, both these viruses target the liver, which is made of functional units called hepatic lobules. The main cells are called hepatocytes. They pick up and detoxify harmful substances like drugs or alcohol; help maintain a normal blood glucose level; synthesize a variety of important proteins, like albumin and coagulation factors; store certain vitamins and some minerals; and convert cholesterol into bile salts, which, along with water and bilirubin, make up the bile.
Hepatitis B virus enters the hepatocytes by fusing its membrane with the cell membrane and releasing the capsid into the cell. The cell's polymerase elongates the shorter strand of the viral DNA, so that it now forms a complete double-stranded DNA with the long strand. It then travels to the nucleus. There, it is transcribed by the cell's transcription elements into multiple mRNAs, which leave the nucleus and use the cell’s ribosomes to create viral proteins, like DNA polymerase and viral antigens: HBs, HB core and HBe antigen. The largest mRNA is used by the viral DNA polymerase to replicate viral DNA. Viral antigens Hbs and Hb core are assembled into new viral particles. Hbe, however, isn’t included in the viral particle, but leaves the cell and can be found in the serum. The viral DNA is replicated and packaged into capsid at the same time, which is why its replication is interrupted and the virus gets partial double-stranded DNA. The capsid is then enveloped and released without damaging the cell, which is why the infection can persist for a long time without causing liver damage.
The damage actually comes from the body's immune system. T-cells find and eliminate infected hepatocytes, which causes liver damage. B-cells react to the virus in the bloodstream and secrete antibodies against hep B antigens. Bilirubin with bile salts is released from the destroyed cells into the bloodstream and impregnates the tissue, causing jaundice, which is a yellowish pigmentation of the skin, mucosa and whites of the eyes. The bile salts get into the skin, and cause itching. The bilirubin from the blood is filtered by the kidneys and ends up in the urine instead of the stool, making it dark, while the stool becomes pale.
An insufficient T-cell response, or, if large amounts of HBs antigen bind to neutralizing antibodies, it can lead to chronic hepatitis. Acute hepatitis B becomes chronic in about 5 to 10% of cases. In some cases, liver damage can progress to scarring, cirrhosis and liver failure. Chronic hepatitis also increases the risk of liver cancer called hepatocellular carcinoma.
Hepatitis D virus enters the cell and the nucleus in the same way. However, it uses the host cell’s RNA polymerase to copy itself and the cell's ribosomes to create delta antigens. Viral RNA is packaged into the capsid, but in order to make a complete viral particle it must use HBs antigen and get enveloped. It then leaves the cell.
Now, delta antigens are harmful to the cell and cause cell death and liver damage, so unlike hep B, hep D damages the cells directly.
Hep D virus causes acute hepatitis in one of two ways. First, there’s co-infection with hep B, when the two viruses infect the liver at the same time; second, there’s superinfection, which is when hep D infects individuals with chronic hepatitis B, which is more severe. Hep D increases the severity of the hep B infection. These individuals are more likely to develop fulminant hepatitis, massive liver necrosis, and hepatic encephalopathy, when the brain function is affected.