Hepatitis B virus
Hepatitis is a malfunction in the liver which is recognised at an acute stage by the occurance of jaundice. Jaundice is the yellowing of the skin and eyeballs, this is caused by a build up in the pigment bilirubin. In a healthy person, haemoglobin from old red blood cells is broken down to bilirubin which is excreted in bile. In a hepatitis patient the liver is infected and bile is not properly metabolised and excreted. Hepatitis can be caused mainly by the picornavirus A and the hepadnavirus B. The other hepatitis causing viruses were termed ‘non-A, non-B hepatitis viruses’, but now are named C,D etc. Hepatitis D virus is a satallite virus of Hepatitis B and needs it present as a helper.
Hepatitis B virus can remain present in the body for years or even a lifetime. It can produce cirrhosis, which is distorted or scarred liver due to the replacement of damaged hepatocytes with fibrous or adipose connective tissue.
Hepatitis B virus (HBV) is the pre-eminent hepadnavirus and is a typical example, it is about 42nm across and is enveloped. HBV has a linear negative sense DNA genome which is linked covalently to a protein at its 5’ end. In addition, the HBV has an incomplete complimentry positive sense strand which overlaps the 5’-3’ junction of the negative sense strand. This causes the genome to be circularised. The negative sense strand is about 3.2 kbp and the positive sense strand is variable betwteen 1700 and 2800 nucleotides long.
When the virus enters the cell, the genome is transported to the nucleus then the capping protein is removed and both the strands are completed and ligated to form the covalently closed circular genome. The host’s RNA polymerase is then used to transcribe the negative strand. The mRNA’s then leave the nucleus. The longest mRNA, which is transcribed more than all the way round the genome encodes a multifunctional polymerase and also serves as a template for genomic DNA synthesis. The polymerase is translated and then interacts with the 5’ end of the mRNA that encoded it and aids in the packaging into virus particles. When packaged, the process of DNA synthesis occurs. The polymerase, which is still attached, is then used as a primer to synthesis the negative sense DNA strand, starting near the 5’ end of the mRNA. This newly sythesised negative sense DNA extends beyond the 5’ end of the mRNA and then complimetry base pairs with the corresponding area on the overlap between the two ends of the mRNA (as mentioned above, the mRNA is transcribed beyond a full circle and overlaps slightly). The negative sense DNA continues to be synthesised. The template is then degraded by RNAse H, all apart from a small section from the 5’ end, which transfers to the repeat corresponding section on the DNA and base pairs. This is then used as a primer for the positive sense DNA strand. The virus usually leaves the cell before the positive sense strand is complete and therefore the truncated version is common.
The HBV genome is very small and therefore the DNA must be used to maximum advantage. Every single nucleotide is used in coding a protein and some are used more than once in separate open reading frames. There are four transcriptional promotors on the HBV genome and there are seven proteins encoded. None of the mRNAare spliced and they all have the same polyadenylation site. Five of the seven proteins are structural C(core), S(surface), M (surface),L(surface) and P(the polymerase mentioned above). M and L are virtually the same as S, they contain only an extended sequence at the 5’ end coding for slightly longer proteins The two nonstructural proteins are X and Pre-C. Pre-c is a protein that is secreted from the cell and known as the e antigen and probably serves to modulate the immune response to the virus. X is a transcriptional activator that is used to take over cellular promoters and regulate viral promotors.
There are estimated to be 300 million infectious carriers worldwide. HBV cannot be grown in culture and so is difficult to analyse and also to produce a vaccine. This problem was overcome using a recombinant clone from yeast. This recombinant vaccine has proved to be very effective. It uses Saccharomyces cervisiae, which has been genetically engineered to express the surface antigen of the HBV, HBsAg. The hepatitis virus vaccine, which is gene cloned costs 80$ or £56 per head for three injections and is unnafordable to 90% of the worlds population including those who the vaccine was designed for. The vaccine is not given as part of a standard programme in the developed world and is only given to those travelling, nurses and the elderly.
Hepatitis B has also been linked to hepatocellular carcinoma. In the parts of the world with high levels of hepititis-B infections, Africa and Southeast Asia, liver cancer is common. The cancer occurs almost exclusively in hepatitis-B sufferers. The world health organisation aims to eradicate hepatitis as part of it’s cancer prevention programme.
Hepatitis B virus is transmitted by sexual contact and contaminated syringes and equipment. It can also be spread by saliva and tears. An effective education programme must be considered to control this virus alongside HIV, also a needle exchange policy, although in the developing world needle’s are reused because they are too expensive to replace.
To summerise, Hepatitis B Virus is a small hepadnavirus about 4.2nm across with a genome about 3.2 kbp. It caused liver failure and even hepatic cancer. Hopefully, in these HIV aware days, because Hepatitis B Virus is transmitted in the same way, we will see a decrease in HBV.
Introduction to Modern Virology – Dimmock, Easton & Leopard
Principles of anatomy and physiology – Tortora / Grabowski
Molecular Biology of the Cell – Alberts et al.
Immunology – Roitt, Bronstoff and Male
Molecular Gentics of Bacteria – Dale