Wednesday, 28 March 2012

The Ebola Virus and Niemann-Pick C1: Towards the Synthesis of a Cure?


By Kim Hanna (41387432)

An electron-microscope image of Ebola-Zaire
(Centers for Disease Control and Prevention 2009)
Ebola is the generic title given to very five similar subtypes of virus, the first of which was discovered during an outbreak in the mid '70s throughout continental Africa. Though the microbiology of Ebola is really quite simple - the virus' genome consists only of a single strand of ribonucleic acid - it has still managed to generate a significant amount of notoriety within the medical and virological worlds as one of the most virulent of diseased that has ever been recorded (Reece et al. 2012).

Three of the five subtypes of Ebola have lead to cases of human death, with these subtypes having a mortality rate of up to ninety percent per individual outbreak, due to the incredibly deleterious effects of viral hemorrhagic fever (Google at your own risk!) The symptoms of an infection are quite varied, but may include both internal and external bleeding, nausea, and muscular pain.   

Perhaps the hardest pill to swallow about Ebola is that there actually is no pill to swallow; there is currently no anti-viral treatment available to combat an infection. However, while a huge amount remains unknown about the ways in which the virus infects host cells, a number of very promising breakthroughs in virological research could potentially lead us towards the synthesis of a future vaccine or cure. 

In early January of this year, medical columnist for The New York Times, Amanda Schaffer, summarised a paper that appeared in Nature, titled "Ebola virus requires the cholesterol transporter Niemann-Pick C1" (Carette et al. 2011). Schaffer's article, "Key protein may give Ebola virus its opening," provides a basic description of the paper's findings, which suggest that the infection mechanism of the Ebola virus has intrinsic links to the cellular presence of a rather unremarkable protein. 

According to Schaffer, researchers working upon a biologically altered, non-lethal form of Ebola have discovered that mice lacking a particular protein known as Niemann-Pick C1 (NPC1) appear entirely immune to the lethal effects of the virus, even after direct exposure. Furthermore, mice that have been genetically engineered to be partially deficient in NPC1 appear far more likely to survive a bout of Ebola infection.

So, what does this all mean?

The Precession of the Trojan Horse in Troy,
Domenico Tiepolo, 1773.
Though the exact molecular interaction between NPC1 and Ebola has not been established, it has been suggested by Dr Karthik Chandran that the protein is required to shuttle the virus from the lysomal membrane into the cytoplasm of the cell, where it can begin replication (Albert College of Medicine 2011). Those that are familiar with the epic poems of Ancient Greece may think of NPC1 as the Trojan horse that appears to bear gifts, but actually harbours great malevolence.

The findings are quite exciting! They provide us with a much clearer image of the ways in which Ebola penetrates into and eventually decimates host cells. Armed with this knowledge, scientists can now target an exact molecule that seems to be key to Ebola infection, and begin some novel research.

For instance, I have since discovered a very recent paper that further proves the link between Ebola and NPC1. Here, the authors propose that a compound which modifies NPC1 within human cells could potentially thwart an otherwise inevitable infection of the virus (Hunt, Lenneman & Maury 2012). This is, of course, much easier said than done, but I find it fascinating to think that changing the transcription, availability or even expression of NPC1 could eventually save countless lives.

Ultimately, while it will be quite some time before we have an effective method to treat Ebola infection, it's reassuring that there have been such critical breakthroughs in the research. Furthermore, for those of us enrolled in BIOL1030, it's great to see that these breakthroughs are being properly communicated to the wider, non-scientific communities through the various forms of mass media.

References

Albert Einstein College of Medicine 2011, Researchers find ‘key’ used by Ebola virus to unlock cells and spread deadly infection, viewed 18 March 2012, http://www.einstein.yu.edu/home/news.asp?id=695.

Carrette, JE, Raaben, M, Wong, AC, Herbert, AS, Obernosterer, G, Mulherkar, N, Kuehne, AI, Kranzusch, PJ, Griffin, AM, Ruthel, G, Dal Cin, P, Dye, JM, Whelan, SP,

Chandran, K & Brummelkamp TR  2012, “Ebola virus entry requires the cholesterol transporter Niemann-Pick C1,” Nature, vol. 477, no. 7364, pp. 340-343.

Hunt, CL, Lennemann, NJ, & Maury, W 2012, “Filovirus entry: a novelty in the viral fusion world,” Viruses, vol. 4, no. 2, pp. 258-275. 

Reece, JB, Meyers, N, Urry LA, Cain, ML, Wasserman, SA, Minorsky, PV, Jackson, RB, & Cooke BN 2012, Campbell Biology, 9th edn, Pearson Australia Group, 

Schaffer, A 2012, Key protein may give Ebola virus its opening, The New York Times, 16 January, viewed 17 March 2012, http://www.nytimes.com/2012/01/17/health/npc1-protein-may-give-ebola-its-opening.htm


World Health Organisation 2012, Ebola haemorrhagic fever, viewed 18 March 2012, http://www.who.int/csr/disease/ebola/en/



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