By: Varun Natraj, Kenneth Forward, and Connor Pennington Semliki Forest Virus Definitions • • • • • • • • • • • • Genome: Set of chromosomes Trimer: A trimer is a polymer with 3 molecules Alphavirus: A mosquito borne virus Icosahedral: Twenty-sided figure Bilayer: Two molecule layer Glycoprotein: Protein with carbohydrate component Capsid: Virus shell Lipid: Constituent of fat Arthropod: Invertebrate animal Interconnective: Mutually connecting Neuropathy: Disease of nervous system Biological Vector: A vector that is vital to the life cycle of a pathogenic cell History/Background • The Semliki Forest Virus was first isolated from mosquitoes in the Semliki Forest in Uganda in 1942. • The Semliki Forest Virus is an Alphavirus; There are a total of 27 alphaviruses able to infect mammals as well as humans. The Semliki Forest Virus is an alphavirus because transmission of the virus occurs via mosquitoes which is a major characteristic of alphaviruses. This makes the alphavirus a contributor to Arthopod borne viruses or Arboviruses. What is the Semliki Forest Virus? • • • • • The Semliki Forest Virus is a positive-stranded RNA based virus with an icosahedral capsid. This is enveloped by a lipid bilayer, constructed from the host cell. The outermost surface of the virus is covered by different monomers of various glycoproteins , which are arranged in interconnective trimers which form the outer shell. The Semliki Forest Virus is spread mainly through mosquito bites. The virus is able to cause massive brain swelling, or encephalitis, in rodents, birds and other small animals, but only one human death has ever been attributed to the virus. However even in this case, the fatality of the victim was caused more so by a faulty immune system and extreme amounts of exposure to the virus rather than the viruses potency. The Virus has been used extensively in biological research as a model of the viral life cycle. Also, due to its broad host range and efficient replication, it has been developed as a vector for genes, encoding vaccines and anti-cancer agents, and as a tool in gene therapy. The Semliki Forest Genome • The size of the Semliki Forest Virus genome is around 13,000 base pairs. • Two-thirds of the genome encode non-structural proteins, while the other third encodes structural proteins. • The expression of these proteins and the replication of the viral chromosomes takes place in the cytoplasm of the host cells. • The composition and transportation of its three glycoproteins through the endoplasmic reticulum and golgi bodies has been used as a model for the synthesis and export of the proteins in the plasma membrane The Semliki Forest Virus, Cancer, and other Diseases • RNA interference is a system within living cells that helps determine what genes are active and how active they are. • RNA interference has recently been discovered as a mode of inhibition for slowly replicating viruses that can cause diseases such as Hepatitis C. • RNA interference has also been tested on SFV to figure out whether RNA interference is a viable option to inhibit rapidly replicating RNA viruses. • Through research scientists have discovered that RNA interference might improve the response to quickly spreading virus based infections. The Semliki Forest Virus, Cancer, and other Diseases cont. • The use of RNA interference has helped prove that faulty genes can lead to cancer. • The knowledge of the structure of the SFV suggests alphaviruses use a common means for infection. This may help in finding possible strategies to help prevent other alphaviruses such as Yellow Fever, and the Dengue Virus. • SFV has been widely used in biological research as a model to illustrate the viral life cycle and to show the effects of the neurological diseases caused by viruses. • SFV has a wide host range and can replicate efficiently; with these characteristics it has been used as a biological vector for genes, encoding vaccines, and cancer agents. The Semliki Forest Virus, Cancer, and other Diseases • Semliki Forest Virus based systems are becoming more prevalent as the virus vector system used for research therapy and diagnosis. They have also been used to formulate vaccines for various pathogens. • For all of these applications of SFV the virus is modified through engineering the viral replicase gene and then targeting specific cell types. • Much of the research done on SFV has been conducted in Europe, through European Union laboratories. Reference • en.wikipedia.org/wiki/Semliki_Forest_Virus • www.liebertonline.com/doi/abs/10.1089/oli.2007.0079 • www.esrf.eu/UsersAndScience/Publications/Highlights/2001/li fe-sciences/LS3 .htm • www.sfvectors.ed.ac.uk/ • medicaldictionary.thefreedictionary.com/Semliki+Forest+Virus • cancerweb.ncl.ac.uk/cgi-bin/omd?Semliki+forest+virus