Semliki Forest virus

{{Short description|Species of virus}}

{{Virusbox

| name = Semliki Forest virus

| image = Semliki-Forest-Virus.jpg

| parent = Alphavirus

| species = Alphavirus semliki

}}

File:Emd-1017.jpg reconstruction of Semliki Forest virus at 9Å resolution (EMDB entry {{PDBe|EMD-1015}}{{Cite journal

| doi = 10.1016/S1097-2765(00)80421-9

| last1 = Mancini | first1 = E. J.

| last2 = Clarke | first2 = M.

| last3 = Gowen | first3 = B. E.

| last4 = Rutten | first4 = T.

| last5 = Fuller | first5 = S. D.

| title = Cryo-electron microscopy reveals the functional organization of an enveloped virus, Semliki Forest virus

| journal = Molecular Cell

| volume = 5

| issue = 2

| pages = 255–266

| year = 2000

| pmid = 10882067

| doi-access = free

}})]]

Semliki Forest virus is an alphavirus found in central, eastern, and southern Africa. It was first isolated from mosquitoes in the Semliki Forest, Uganda by the Uganda Virus Research Institute in 1942 and described by Smithburn and Haddow.{{cite journal | last1 = Smithburn | first1 = KC | last2 = Haddow | first2 = AJ | year = 1944 | title = Semliki Forest Virus I. Isolation and Pathogenic Properties | journal = J. Immunol. | volume = 49 | pages = 141–157 | doi = 10.4049/jimmunol.49.3.141 }} It is known to cause disease in animals and humans.

The Semliki Forest virus is a positive-strand RNA virus with a genome of approximately 13,000 base pairs which encodes nine proteins.{{Cite journal

| last1 = Atkins | first1 = G. J.

| last2 = Sheahan | first2 = B. J.

| last3 = Liljeström | first3 = P.

| title = The molecular pathogenesis of Semliki Forest virus: A model virus made useful?

| journal = The Journal of General Virology

| volume = 80

| pages = 2287–2297

| year = 1999

| pmid = 10501479

| issue=9

| doi=10.1099/0022-1317-80-9-2287

| doi-access = free

}} 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 capsid, which is enveloped by a lipid bilayer derived from the host cell. The outermost surface of the virus is almost entirely covered by heterodimers of glycoproteins 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.

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 mammals through inhalation or gastrointestinal exposure, although rodents in the laboratory can be infected by intranasal instillation. The virus is able to cause a lethal encephalitis in rodents,{{Cite journal

| doi = 10.1099/0022-1317-66-3-395

| last1 = Atkins | first1 = G. J.

| last2 = Sheahan | first2 = B. J.

| last3 = Dimmock | first3 = N. J.

| title = Semliki Forest virus infection of mice: A model for genetic and molecular analysis of viral pathogenicity

| journal = The Journal of General Virology

| volume = 66

| issue = 3

| pages = 395–408

| year = 1985

| pmid = 2982998

| doi-access = free

}} but generally only mild symptoms in humans.{{Cite journal

| last1 = Mathiot | first1 = C. C.

| last2 = Grimaud | first2 = G.

| last3 = Garry | first3 = P.

| last4 = Bouquety | first4 = J. C.

| last5 = Mada | first5 = A.

| last6 = Daguisy | first6 = A. M.

| last7 = Georges | first7 = A. J.

| title = An outbreak of human Semliki Forest virus infections in Central African Republic

| journal = The American Journal of Tropical Medicine and Hygiene

| volume = 42

| issue = 4

| pages = 386–393

| year = 1990

| pmid = 2158754

| doi = 10.4269/ajtmh.1990.42.386

}} Only one lethal human infection has been reported. In this one case, the patient was speculated to be immunodeficient and potentially had been exposed to large amounts of virus in the laboratory.{{Cite journal

| doi = 10.1126/science.424742

| last1 = Willems | first1 = W. R.

| last2 = Kaluza | first2 = G.

| last3 = Boschek | first3 = C. B.

| last4 = Bauer | first4 = H.

| last5 = Hager | first5 = H.

| last6 = Schütz | first6 = H. J.

| last7 = Feistner | first7 = H.

| title = Semliki forest virus: Cause of a fatal case of human encephalitis

| journal = Science

| volume = 203

| issue = 4385

| pages = 1127–1129

| year = 1979

| pmid = 424742

| bibcode = 1979Sci...203.1127W }}

Semliki Forest virus has been used extensively in biological research as a model 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 for genes encoding vaccines and anti-cancer agents,{{Cite journal

| last1 = Quetglas | first1 = J. I.

| last2 = Ruiz-Guillen | first2 = M.

| last3 = Aranda | first3 = A.

| last4 = Casales | first4 = E.

| last5 = Bezunartea | first5 = J.

| last6 = Smerdou | first6 = C.

| doi = 10.1016/j.virusres.2010.07.027

| title = Alphavirus vectors for cancer therapy

| journal = Virus Research

| volume = 153

| issue = 2

| pages = 179–196

| year = 2010

| pmid = 20692305

}} and as a tool in gene therapy.{{Cite journal

| last1 = Lundstrom | first1 = K.

| title = Semliki Forest virus vectors for gene therapy

| doi = 10.1517/14712598.3.5.771

| journal = Expert Opinion on Biological Therapy

| volume = 3

| issue = 5

| pages = 771–777

| year = 2003

| pmid = 12880377

}}

Since Semliki Forest virus naturally infects cells of the central nervous system, it has been pre-clinically tested as an oncolytic virus against the very aggressive brain tumour type glioblastoma. The virus was genetically modified with microRNA 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.{{Cite journal|last1=Ramachandran|first1=Mohanraj|last2=Yu|first2=Di|last3=Essand|first3=Magnus|year=2016|title=Safe and effective treatment of experimental neuroblastoma and glioblastoma using systemically administered triple microRNA-detargeted oncolytic Semliki Forest virus.|journal=Clinical Cancer Research|publication-date=2016-09-16|volume=23|issue=6|pages=1519–1530|doi=10.1158/1078-0432.CCR-16-0925|pmid=27637889|doi-access=free}} The modified virus was also found to efficiently kill human glioblastoma tumour cell lines.

{{External media

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| width =230px

| video1 =[https://www.youtube.com/watch?v=G4sQBrrs8gA&index=64&list=PL058E6F6BDEA23661&t=13m18s Semliki Forest virus entry. 3 min.] }}