The Semliki Forest virus is an

alphavirus ''Alphavirus'' is a genus of RNA viruses, the sole genus in the ''Togaviridae'' family. Alphaviruses belong to group IV of the Baltimore classification of viruses, with a positive-sense, single-stranded RNA genome. There are 32 alphaviruses ...

found in central, eastern, and southern

Africa Africa is the world's second-largest and second-most populous continent, after Asia in both cases. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 6% of Earth's total surface area ...

. It was first isolated from

mosquito Mosquitoes (or mosquitos) are members of a group of almost 3,600 species of small flies within the family Culicidae (from the Latin ''culex'' meaning " gnat"). The word "mosquito" (formed by ''mosca'' and diminutive ''-ito'') is Spanish for "li ...

es in the Semliki Forest,

Uganda }), is a landlocked country in East Africa East Africa, Eastern Africa, or East of Africa, is the eastern subregion of the African continent. In the United Nations Statistics Division scheme of geographic regions, 10-11-(16*) territor ...

by the

Uganda Virus Research Institute The Uganda Virus Research Institute (UVRI) is a medical research institute owned by the Uganda government that carries out research on communicable diseases in man and animals, with emphasis on viral transmitted infections. UVRI is a component of ...

in 1942 and described by Smithburn and Haddow. It is known to cause disease in animals including humans. The Semliki Forest virus is a

positive-strand RNA virus Positive-strand RNA viruses (+ssRNA viruses) are a group of related viruses that have positive-sense, single-stranded genomes made of ribonucleic acid. The positive-sense genome can act as messenger RNA (mRNA) and can be directly translated int ...

with a

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

of approximately 13,000

base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

s which encodes nine

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

s. The 5’ two thirds of the genome encode four non-structural proteins concerned with RNA synthesis; the structural proteins are encoded in the 3’ one third. Of the structural proteins, the C proteins make up the

icosahedral In geometry, an icosahedron ( or ) is a polyhedron with 20 faces. The name comes and . The plural can be either "icosahedra" () or "icosahedrons". There are infinitely many non- similar shapes of icosahedra, some of them being more symmetrica ...

capsid A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may ...

, which is enveloped by a

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...

bilayer derived from the host cell. The outermost surface of the virus is almost entirely covered by heterodimers of

glycoproteins Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

E1 and E2, arranged in interconnective trimers, which form an outer shell. Trimers are anchored in the membrane by an E2 cytoplasmic domain that associates with the

nucleocapsid A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may ...

. Replication occurs via a negative strand intermediate giving rise to a full length genomic RNA for export in new virions and a subgenomic message that is translated into the structural proteins. Semliki Forest virus is spread mainly by mosquito bites. It is not able to infect

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

s through

inhalation Inhalation (or Inspiration) happens when air or other gases enter the lungs. Inhalation of air Inhalation of air, as part of the cycle of breathing, is a vital process for all human life. The process is autonomic (though there are exceptions ...

gastrointestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

exposure, although

rodent Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia (), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are na ...

s in the laboratory can be infected by intranasal instillation. The virus is able to cause a lethal

encephalitis Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, ...

in rodents, but generally only mild symptoms in humans. Only one lethal human infection has been reported. In this one case, the patient was speculated to be

immunodeficient Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...

and potentially had been exposed to large amounts of virus in the laboratory. Semliki Forest virus has been used extensively in biological research as a

model A model is an informative representation of an object, person or system. The term originally denoted the plans of a building in late 16th-century English, and derived via French and Italian ultimately from Latin ''modulus'', a measure. Models c ...

of the viral life cycle and of viral neuropathy. Due to its broad host range and efficient replication, it has also been developed as a

vector Vector most often refers to: *Euclidean vector, a quantity with a magnitude and a direction *Vector (epidemiology), an agent that carries and transmits an infectious pathogen into another living organism Vector may also refer to: Mathematic ...

for

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

s encoding

vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...

s and anti-

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

agents, and as a tool in

gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...

. Since Semliki Forest virus naturally infects cells of the central nervous system, it has been pre-clinically tested as an

oncolytic virus An oncolytic virus is a virus that preferentially infects and kills cancer cells. As the infected cancer cells are destroyed by lysis#Oncolysis, oncolysis, they release new infectious virus particles or virus, virions to help destroy the remaining ...

against the very aggressive brain tumour type

glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...

. The SFV virus was genetically modified with

microRNA MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...

target sequences so that it only replicated in brain tumour cells and not in normal brain cells. The modified virus reduced tumour growth and prolonged survival of mice with brain tumours. The modified virus was also found to efficiently kill human glioblastoma tumour

cell line An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cell ...

References

* * {{Taxonbar, from=Q428413 Alphaviruses

See also

References