Sunday, July 6, 2008

The Epstein Barr Virus

I have another blog. It is Yeah, I actually expected people to remember that. Anyway, I have begun transferring some of my articles from that blog to this one. xiphus is a nice name, isn't it? It's easy to remember at any rate.

Epstein Barr Virus (family: Herpesviridae) is an enveloped, ds-DNA (approx. 185kbp genome) virus that is the causative agent of numerous diseases such as Infectious Mononucleosis and Multiple Sclerosis. However, it is also known to cause Burkitt’s Lymphoma in developing countries (esp. Africa). Indeed, EBV was the first oncogenic virus to be discovered.
Primary infections occur through oral secretions (kissing, etc.). The infection is initially limited to the oral mucosa. It subsequently infects the B-cells using the CD-21 receptor (a member of the Immunoglobulin family highly expressed in B cells) and transforms them to replicate repeatedly. Indeed, the assay used for EBV is to check its ability to immortalise B lymphocytes from EBV- individuals. Immortalising B-lymphocytes is a function of the EBNA-2 gene.
Thus, EBNA-2 transforms the B-cells and makes them reproduce in an uncontrolled manner. This is the reason, we find that mononuclear lymphocytes predominate in Infectious mononucleosis. The gene also regulates the size of the antigenic site. Consequently, “Ebnotyping” has been considered as a method of classifying EBV. In fact, this has been used to show that the bone marrow is the initial site of infection. This is supported by the observation that people, who received a bone marrow transplant, lost their own ebnotype and gained the donor’s.
Following infection, most cells don’t express the entire genome to replicate. Instead, the origin of plasmid replication (oriP) gene (1.7 kbp long) enables autonomous, extrachromosomal replication. The EBNA-1 gene has also been implicated in the maintenance of the episome because in EBNA-1 deficient mutants, the virus gets integrated in the host’s genome. This gene shares the same promoter as EBNA-2 and helps to recruit the cell’s DNA replication machinery. Most cells replicate once per host cell division. A small proportion, however, does enter the lytic cycle and produce multiple copies.
The lytic cycle is controllef by a protein called oriLyt. It is aided in this function by BHLF-1 and BZLF-1. In latently infected cells, the cell division occurs at the rate of one division per 30 minutes. On the other hand, a cell in the lytic cycle produces 1000 copies per cell. All herpes viruses produce DNA concatemers. EBV is no exception.
Epstein Barr virus was first isolated from a Burkitt’s Lymphoma tumour. This disease is the fastest progressing Non-Hodgkin’s lymphoma that occurs in children due to the translocation of the myc gene (a protooncogene; normally codes for transcription factors) from chromosome 8 to chromosome 14. It has been widely accepted that this may be due to a weakened immune system created by a simultaneous chronic malarial infection.
Interestingly, EBV may mimic cellular functions to evade the scrutiny of the marauding immunosurveillance system. Indeed, stunning similarities have been noted between Interluken-10 (a mouse cytokine) and a viral protein called BRCF-1. This is a most remarkable aspect of the EBV. It is possibly the most successful parasite in the world since it stays latent in 90% of the human population throughout their entire life. You have it in you right now!

1 comment:

The Wanderer said...

Goodness me Sonu! That thought of probably being one of 90% individuals that have a latent EBV in them sure gave me the shivers after having read all that you had to write about it - pretty dangerous virus that, if it can act as an oncogen... The level of latency, the masking effect it has and the virus' potential to do damage reminds me of the bit regarding not being able to see a dangerous enemy (and how that is scarier than being informed of the enemy's presence)!

Nonetheless, a well-written article indeed. Carry on the good work :-)