Hello everyone and welcome to this week's blog post, which is the first in a two-part series about the Epstein-Barr virus! In this article, I will be using the Epstein-Barr virus as an example to define what makes a perfect virus. Next week, I will discuss the diseases caused by this virus, including mono and some types of cancer.
Sometimes referred to as the 'perfect virus', the Epstein-Barr Virus is a member of the herpes virus family and is one of the most common viruses globally. Indeed, one paper estimated that at least 95% of the world population is infected with the virus. In this article, I will explore what makes the virus so 'perfect', the symptoms and diagnosis of diseases associated with its infection and how the disease can be prevented and cured.
I propose that in order for a virus to survive, 3 conditions must be true. Firstly, the virus must have hosts between whom the virus can spread. Secondly, it must be able to affect the immune system. However, the virus can't simply destroy the immune system. It needs to weaken the immune system enough to avoid destruction, but not enough to kill the host (i.e. the virus can't weaken the immune system so much that it causes the person to die from another infection). This is very important as if the host is killed, then the virus can no longer be transmitted and the virus will eventually die out. Thirdly, the virus must have a high rate of replication. I will address each of these conditions in turn and explain how they are optimised by the Epstein-Barr Virus.
Firstly, the virus must have hosts it can infect and be able to spread between the hosts easily. We know that the virus is able to infect humans, meaning that it has a large population it can infect. The virus also is extremely virulent. The Ebstein-Barr Virus is transmitted by bodily fluids, especially through saliva. As such, according to the United States Center for Disease Control, the virus can spread by kissing, sharing drinks and food and having contact with toys that children have drooled over. In addition, the virus can also spread through blood transfusions, sexual contact, sharing needles and organ transplants. The virus can also survive outside of hosts, particularly on moist surfaces, which increases its transmission. Therefore, clearly the first of these conditions is met.
The second condition for a virus to be 'perfect' is that it can affect the hosts' immune system and other bodily functions. It needs to do this both to increase the likelihood of its survival and increase the likelihood it will spread to another host (e.g. by sneezing). The Epstein-Barr virus is very effective in doing this. Like all viruses, the Epstein-Barr virus must enter somatic cells in order to replicate, since they don't have the cell machinery to do this.
Following primary infection, the Epstein-Barr virus infects both epithelial cells and B-lymphocyte cells. Not only does this allow the virus to be concealed from the immune system for some time, but according to a paper published in 2011, it also allows it to evade the immune system later during the infection. This is because, following the infection of B-lymphocyte cells, the virus can produce antigens and other proteins, which are used for immune evasion.
Moreover, the virus triggers infected B-lymphocytes to differentiate forming memory cells that are also infected by the virus. Since these cells are part of your own immune system, it is much harder to destroy them and thus destroy the infection. Additionally, memory cells are produced in such vast quantities that scientists predict that, following infection, the host will always have memory cells infected with the Epstein-Barr virus.
Due to the fact that these memory cells remain in the body for such a long time, most people after having being infected by the virus remain latently infected for life. Consequently, while the virus isn't actively spreading around the body if the immune system is compromised (e.g. due to the use of immunosuppressant drugs following organ transplantation) then the infection can quickly start up again.
Considering how the Epstein-Barr virus is able to avoid the host immune system and hijack memory cells to lengthen the duration of infection, we can conclude that the second condition for a 'perfect virus' is met by the Epstein-Barr virus.
The third condition was that the virus must have a high rate of replication. Viruses can replicate by two different mechanisms - the lytic cycle and the lysogenic cycle. The Epstein-Barr virus can replicate both by lytic replication and by lysogenic replication (in B-lymphocyte cells).
In both types of replication, the Epstein-Barr virus enters the host cell and the viral capsid dissolves. The genome of the virus is then transported to the nucleus of the cell. The virus's DNA transcribes itself to produce messenger RNA chains. These mRNA molecules are then read by the ribosomes in the cell. Translation then occurs, where the ribosomes manufacture viral proteins instead of the host's proteins. These proteins then form new viruses. Following lysis of the host cell, where the cell disintegrates, these new viruses are released into the host and infect other cells.
In lysogenic replication, the virus DNA is incorporated within the host DNA, allowing the virus to remain dormant in the host cell without killing the cell. As I mentioned above, this happens when the Epstein-Barr virus infects B-lymphocytes. While this mechanism for replication is potentially safer for the virus as it means the host can't be killed before the virus can spread, the lysogenic method for replication is extremely slow. Meanwhile, the lytic mechanism of replication is much faster, producing much larger large quantities of the virus, which increases the chance of the virus spreading.
By incorporated both mechanisms for replication, the Epstein-Barr virus is able to produce large quantities of the virus, increasing the chance that the virus will spread, and is also able to store a copy of its genome inside the host cells, thus preventing the virus from being destroyed completely by the immune system and allowing it to resurge when the immune system is later weakened. Therefore, I would contend that the Epstein-Barr virus fulfils this third condition.
In conclusion, we can see that the Epstein-Barr virus can be defined as a 'perfect virus'. It can infect the entire human population of 7.8 billion people, giving it a large number of hosts, and can spread through bodily fluids between hosts easily. Additionally, the virus also doesn't kill its hosts, allowing it to spread without dying out. The virus is also able to hide from the body's own immune system and lie dormant in memory cells so that it can't be fully destroyed even by a strong immune system. It can also replicate quickly to overwhelm the immune system.
I hope you enjoyed this week's article. While the Epstein-Barr virus does not cause disease in the vast majority of people whom it infects, it can cause some diseases regardless. Make sure to subscribe to notifications so that you get notified when next week's article about these diseases gets published.
Sources:
Cohen JI. Optimal treatment for chronic active Epstein-Barr virus disease.Pediatr Transplant. 2009;13(4):393‐396. doi:10.1111/j.1399-3046.2008.01095.x
Jha HC, Pei Y, Robertson ES. Epstein-Barr Virus: Diseases Linked to Infection and Transformation.Front Microbiol. 2016;7:1602. Published 2016 Oct 25. doi:10.3389/fmicb.2016.01602
Odumade OA, Hogquist KA, Balfour HH Jr. Progress and problems in understanding and managing primary Epstein-Barr virus infections.Clin Microbiol Rev. 2011;24(1):193‐209. doi:10.1128/CMR.00044-10
Hadinoto V, Shapiro M, Greenough TC, Sullivan JL, Luzuriaga K, Thorley-Lawson DA. On the dynamics of acute EBV infection and the pathogenesis of infectious mononucleosis.Blood. 2008;111(3):1420‐1427. doi:10.1182/blood-2007-06-093278
Tsurumi, T., Fujita, M., & Kudoh, A. (2004). Latent and lytic Epstein-Barr virus replication strategies.Reviews In Medical Virology,15(1), 3-15. doi: 10.1002/rmv.441
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