In biology and immunology, an Alphavirus belongs to group IV of the Baltimore classification of the Togaviridae family of viruses, according to the system of classification based on viral genome composition introduced by David Baltimore in 1971. Alphaviruses, like all other group IV viruses, have a positive sense, single-stranded RNA genome. There are thirty alphaviruses able to infect various vertebrates such as humans, rodents, fish, birds, and larger mammals such as horses as well as invertebrates. Transmission between species and individuals occurs mainly via mosquitoes, making the alphaviruses a member of the collection of arboviruses – or arthropod-borne viruses. Alphavirus particles are enveloped, have a 70 nm diameter, tend to be spherical (although slightly pleomorphic), and have a 40 nm isometric nucleocapsid.[1]

A computer-generated model of the surface of an "Alphavirus" derived by cryoelectron microscopy. The spike-like structures on the virion surface are trimers composed of heterodimers of the virion surface glycoproteins E1 and E2. These spikes are used by the virus to attach to susceptible animal cells
A computer-generated model of the surface of an Alphavirus derived by cryoelectron microscopy. The spike-like structures on the virion surface are trimers composed of heterodimers of the virion surface glycoproteins E1 and E2. These spikes are used by the virus to attach to susceptible animal cells
Virus classification
(unranked): Virus
Realm: Riboviria
(unranked): incertae sedis
Family: Togaviridae
Genus: Alphavirus
Type species
Sindbis virus


PDB 1rer EBI
crystal structure of the homotrimer of fusion glycoprotein e1 from semliki forest virus.
OPM superfamily109
OPM protein1rer
PDB 1z8y EBI
mapping the e2 glycoprotein of alphaviruses
OPM superfamily109
OPM protein2yew
OPM superfamily109

The alphaviruses are small, spherical, enveloped viruses with a genome of a single positive sense strand RNA. The total genome length ranges between 11,000 and 12,000 nucleotides, and has a 5’ cap, and 3’ poly-A tail. The four non-structural protein genes are encoded in the 5′ two-thirds of the genome, while the three structural proteins are translated from a subgenomic mRNA colinear with the 3′ one-third of the genome.

There are two open reading frames (ORF’s) in the genome, non-structural and structural. The first is non structural and encodes proteins (nsP1–nsP4) necessary for transcription and replication of viral RNA. The second encodes three structural proteins: the core nucleocapsid protein C, and the envelope proteins P62 and E1 that associate as a heterodimer. The viral membrane-anchored surface glycoproteins are responsible for receptor recognition and entry into target cells through membrane fusion.

Structural proteins

The proteolytic maturation of P62 into E2 and E3 causes a change in the viral surface. Together the E1, E2, and sometimes E3, glycoprotein "spikes" form an E1/E2 dimer or an E1/E2/E3 trimer, where E2 extends from the centre to the vertices, E1 fills the space between the vertices, and E3, if present, is at the distal end of the spike.[2] Upon exposure of the virus to the acidity of the endosome, E1 dissociates from E2 to form an E1 homotrimer, which is necessary for the fusion step to drive the cellular and viral membranes together. The alphaviral glycoprotein E1 is a class II viral fusion protein, which is structurally different from the class I fusion proteins found in influenza virus and HIV. The structure of the Semliki Forest virus revealed a structure that is similar to that of flaviviral glycoprotein E, with three structural domains in the same primary sequence arrangement.[3] The E2 glycoprotein functions to interact with the nucleocapsid through its cytoplasmic domain, while its ectodomain is responsible for binding a cellular receptor. Most alphaviruses lose the peripheral protein E3, but in Semliki viruses it remains associated with the viral surface.

Non structural proteins

Four nonstructural proteins (nsP1–4) which are produced as a single polyprotein constitute the virus' replication machinery.[4] The processing of the polyprotein occurs in a highly regulated manner, with cleavage at the P2/3 junction influencing RNA template use during genome replication. This site is located at the base of a narrow cleft and is not readily accessible. Once cleaved nsP3 creates a ring structure that encircles nsP2. These two proteins have an extensive interface.

Mutations in nsP2 that produce noncytopathic viruses or a temperature sensitive phenotypes cluster at the P2/P3 interface region. P3 mutations opposite the location of the nsP2 noncytopathic mutations prevent efficient cleavage of P2/3. This in turn affects RNA infectivity altering viral RNA production levels.


The virus has a 60–70 nanometer diameter. It is enveloped, spherical and has a positive-strand RNA genome of ~12 kilobases. The genome encodes two polyproteins. The first polyprotein consists of four non-structural units: in order from the N terminal to the C terminal - nsP1, nsP2, nsP3, and nsP4. The second is a structural polyprotein composed of five expression units: from the N terminal to the C terminal - Capsid, E3, E2, 6K and E1. A sub genomic positive strand RNA - the 26S RNA - is replicated from a negative-stranded RNA intermediate. This serves as template for the synthesis of viral structural proteins. Most alphaviruses have conserved domains involved in regulation of viral RNA synthesis.

The nucleocapsid, 40 nanometers in diameter, contains 240 copies of the capsid protein and has a T = 4 icosahedral symmetry. The E1 and E2 viral glycoproteins are embedded in the lipid bilayer. Single E1 and E2 molecules associate to form heterodimers. The E1–E2 heterodimers form one-to-one contacts between the E2 protein and the nucleocapsid monomers. The E1 and E2 proteins mediate contact between the virus and the host cell.

Several receptors have been identified. These include prohibitin, phosphatidylserine, glycosaminoglycans and ATP synthase β subunit.

Replication occurs within the cytoplasm and virions mature by budding through the plasma membrane, where virus-encoded surface glycoproteins E2 and E1 are assimilated.

These two glycoproteins are the targets of numerous serologic reactions and tests including neutralization and hemagglutination inhibition. The alphaviruses show various degrees of antigenic cross-reactivity in these reactions and this forms the basis for the seven antigenic complexes, 30 species and many subtypes and varieties. The E2 protein is the site of most neutralizing epitopes, while the E1 protein contains more conserved, cross-reactive epitopes.


A study of this taxon suggests that this group of viruses had a marine origin—specifically the Southern Ocean—and that they have subsequently spread to both the Old and New World.[5]

There are three subgroups in this genus: the Semliki Forest virus subgroup (Semliki Forest, O'nyong-nyong and Ross River viruses); the eastern equine encephalitis virus subgroup (eastern equine encephalitis and Venezuelan equine encephalitis viruses) and the Sindbis virus subgroup.[6] Sindbis virus, geographically restricted to the Old World, is more closely related to the eastern equine encephalitis subgroup, which are New World viruses, than it is to the Semliki Forest virus subgroup which is also found in the Old World.


Group: ssRNA(+)


The seven complexes are:

Barmah Forest virus complex
Barmah Forest virus
Eastern equine encephalitis complex
Eastern equine encephalitis virus (seven antigenic types)
Middelburg virus complex
Middelburg virus
Ndumu virus complex
Ndumu virus
Semliki Forest virus complex
Bebaru virus
Chikungunya virus
Getah virus
Mayaro virus
Subtype: Una virus
O'nyong'nyong virus
Subtype: Igbo-Ora virus
Ross River virus
Subtype: Sagiyama virus
Semliki Forest virus
Subtype: Me Tri virus
Venezuelan equine encephalitis complex
Cabassou virus
Everglades virus
Mosso das Pedras virus
Mucambo virus
Paramana virus
Pixuna virus
Rio Negro virus
Trocara virus
Subtype: Bijou Bridge virus
Venezuelan equine encephalitis virus
Western equine encephalitis complex
Aura virus
Babanki virus
Kyzylagach virus
Sindbis virus
Ockelbo virus
Whataroa virus
Recombinants within this complex
Buggy Creek virus
Fort Morgan virus
Highlands J virus
Western equine encephalitis virus
Eilat virus
Mwinilunga alphavirus
Salmon pancreatic disease virus
Rainbow trout sleeping disease virus
Southern elephant seal virus
Tonate virus


Barmah Forest virus is related to the Semliki Forest virus. Middelburg virus, although classified as a separate complex, may be a member of the Semliki Forest virus group.

It seems likely that the genus evolved in the Old World from an insect-borne plant virus.[8]

Sindbis virus may have originated in South America.[9] The equine encephalitis viruses and the Sindbis virus are related.

The Old World and New World viruses appears to have diverged between 2000 and 3000 years ago.[10] Divergence between the Venezuelan equine encephalitis virus and the eastern equine virus appears to have been ~1400 years ago.[11]

The fish infecting clade appears to be basal to the other species.

The southern elephant seal virus appears to be related to the Sinbis clade.

Pathogenesis and immune response

Medically important alphaviruses
Virus Human Disease Vertebrate Reservoir Distribution
Barmah Forest virus Fever, malaise, rash, joint pain, muscle tenderness Humans Australia
Chikungunya virus Rash, arthritis Primates, humans Africa, Latin America, India, SE Asia
Mayaro virus Rash, arthritis Primates, humans South America
O'nyong'nyong virus Rash, arthritis Primates, Humans Africa
Ross River virus Rash, arthritis Mammals, humans Australia, South Pacific
Semliki Forest virus Rash, arthritis Birds Africa
Sindbis virus Rash, arthritis Birds Europe, Africa, Australia
Una virus Rash, arthritis Primates, humans South America
Eastern equine encephalitis virus Encephalitis Birds Americas
Tonate virus Encephalitis Humans South America
Venezuelan equine encephalitis virus Encephalitis Rodents, horses Americas
Western equine encephalitis virus Encephalitis Birds, mammals North America

There are many alphaviruses distributed around the world with the ability to cause human disease. Infectious arthritis, encephalitis, rashes and fever are the most commonly observed symptoms. Larger mammals such as humans and horses are usually dead-end hosts or play a minor role in viral transmission; however, in the case of Venezuelan equine encephalitis the virus is mainly amplified in horses. In most other cases the virus is maintained in nature in mosquitoes, rodents and birds.

Alphavirus infections are spread by insect vectors such as mosquitoes. Once a human is bitten by the infected mosquito, the virus can gain entry into the bloodstream, causing viremia. The alphavirus can also get into the CNS where it is able to grow and multiply within the neurones. This can lead to encephalitis, which can be fatal.

When an individual is infected with this particular virus, its immune system can play a role in clearing away the virus particles. Alphaviruses are able to cause the production of interferons. Antibodies and T cells are also involved. The neutralizing antibodies also play an important role to prevent further infection and spread.

Diagnosis, prevention, and control

Diagnoses is based on clinical samples from which the virus can be easily isolated and identified. There are no alphavirus vaccines currently available. Vector control with repellents, protective clothing, breeding site destruction, and spraying are the preventive measures of choice.


Alphaviruses are of interest to gene therapy researchers, in particular the Ross River virus, Sindbis virus, Semliki Forest virus, and Venezuelan equine encephalitis virus have all been used to develop viral vectors for gene delivery. Of particular interest are the chimeric viruses that may be formed with alphaviral envelopes and retroviral capsids. Such chimeras are termed pseudotyped viruses. Alphaviral envelope pseudotypes of retroviruses or lentiviruses are able to integrate the genes that they carry into the expansive range of potential host cells that are recognized and infected by the alphaviral envelope proteins E2 and E1. The stable integration of viral genes is mediated by the retroviral interiors of these vectors. There are limitations to the use of alphaviruses in the field of gene therapy due to their lack of targeting, however, through the introduction of variable antibody domains in a non-conserved loop in the structure of E2, specific populations of cells have been targeted. Furthermore, the use of whole alphaviruses for gene therapy is of limited efficacy both because several internal alphaviral proteins are involved in the induction of apoptosis upon infection and also because the alphaviral capsid mediates only the transient introduction of mRNA into host cells. Neither of these limitations extend to alphaviral envelope pseudotypes of retroviruses or lentiviruses. However, the expression of Sindbis virus envelopes may lead to apoptosis, and their introduction into host cells upon infection by Sindbis virus envelope pseudotyped retroviruses may also lead to cell death. The toxicity of Sindbis viral envelopes may be the cause of the very low production titers realized from packaging cells constructed to produce Sindbis pseudotypes. Another branch of research involving alphaviruses is in vaccination. Alphaviruses are apt to be engineered to create replicon vectors which efficiently induce humoral and T-cell immune responses. They could therefore be used to vaccinate against viral, bacterial, protozoan, and tumor antigens.

See also


  • Alphavirus vectors: from protein production to gene therapy, C Smerdou & P Liljestrom, Gene Therapy and Regulation Vol 1 No 1 2000 pp. 33–63
  • Rayner, Jonathan O; Dryga, Sergey A; Kamrud, Kurt I (2002). "Alphavirus vectors and vaccination". Reviews in Medical Virology. 12 (5): 279–296. doi:10.1002/rmv.360. PMID 12211042.


  1. ^ Chen, R; Mukhopadhyay, S; Merits, A; Bolling, B; Nasar, F; Coffey, LL; Powers, A; Weaver, SC; Ictv Report, Consortium (June 2018). "ICTV Virus Taxonomy Profile: Togaviridae". The Journal of General Virology. 99 (6): 761–762. doi:10.1099/jgv.0.001072. PMID 29745869.
  2. ^ Vénien-Bryan C, Fuller SD (February 1994). "The organization of the spike complex of Semliki Forest virus". J. Mol. Biol. 236 (2): 572–83. doi:10.1006/jmbi.1994.1166. PMID 8107141.
  3. ^ Lescar J, Roussel A, Wien MW, Navaza J, Fuller SD, Wengler G, Wengler G, Rey FA (April 2001). "The Fusion glycoprotein shell of Semliki Forest virus: an icosahedral assembly primed for fusogenic activation at endosomal pH". Cell. 105 (1): 137–48. doi:10.1016/S0092-8674(01)00303-8. PMID 11301009.
  4. ^ Shin G, Yost SA, Miller MT, Elrod EJ, Grakoui A, Marcotrigiano J (2012) Structural and functional insights into alphavirus polyprotein processing and pathogenesis. Proc Natl Acad Sci USA
  5. ^ Forrester NL, Palacios G, Tesh RB, Savji N, Guzman H, Sherman M, Weaver SC, Lipkin WI (December 2011). "Genome scale phylogeny of the Alphavirus genus suggests a marine origin". J Virol. 86 (5): 2729–38. doi:10.1128/JVI.05591-11. PMC 3302268. PMID 22190718.
  6. ^ Levinson RS, Strauss JH, Strauss EG (1990). "Complete sequence of the genomic RNA of O'nyong-nyong virus and its use in the construction of alphavirus phylogenetic trees". Virology. 175 (1): 110–123. doi:10.1016/0042-6822(90)90191-s.
  7. ^ "ICTV Report Togaviridae".
  8. ^ Powers AM, Brault AC, Shirako Y, Strauss EG, Kang W, Strauss JH, Weaver SC (November 2001). "Evolutionary relationships and systematics of the alphaviruses". J. Virol. 75 (21): 10118–31. doi:10.1128/JVI.75.21.10118-10131.2001. PMC 114586. PMID 11581380.
  9. ^ Lundström JO, Pfeffer M (November 2010). "Phylogeographic structure and evolutionary history of Sindbis virus". Vector Borne Zoonotic Dis. 10 (9): 889–907. doi:10.1089/vbz.2009.0069. PMID 20420530.
  10. ^ Weaver SC, Hagenbaugh A, Bellew LA, Netesov SV, Volchkov VE, Chang GJ, Clarke DK, Gousset L, Scott TW, Trent DW (November 1993). "A comparison of the nucleotide sequences of eastern and western equine encephalomyelitis viruses with those of other alphaviruses and related RNA viruses". Virology. 197 (1): 375–90. doi:10.1006/viro.1993.1599. PMID 8105605.
  11. ^ Weaver SC, Rico-Hesse R, Scott TW (1992). "Genetic diversity and slow rates of evolution in New World alphaviruses". Curr. Top. Microbiol. Immunol. 176: 99–117. PMID 1318187.

External links

Alphavirus infection

Alphavirus infection may be caused by a Sindbis virus infection, and result in a cutaneous eruption of multiple, erythematous, 4- to 4-mm papules.

Babanki virus

Babanki virus (BBKV) is a member of the virus family Togaviridae of Class IV of the Baltimore classification system and the genus Alphavirus.

Brome mosaic virus

Brome mosaic virus (BMV) is a small (28 nm, 86S), positive-stranded, icosahedral RNA plant virus belonging to the genus Bromovirus, family Bromoviridae, in the Alphavirus-like superfamily.

BMV was first isolated in 1942 from bromegrass (Bromus inermis), had its genomic organization determined by the 1970s, and was completely sequenced with commercially available clones by the 1980s.The alphavirus-like superfamily includes more than 250 plant and animal viruses including Tobacco mosaic virus, Semliki forest virus, Hepatitis E virus, Sindbis virus, and arboviruses (which cause certain types of encephalitis). Many of the positive-strand RNA viruses that belong to the alphavirus family share a high degree of similarity in proteins involved in genomic replication and synthesis. The sequence similarities of RNA replication genes and strategies for BMV have been shown to extend to a wide range of plant and animal viruses beyond the alphaviruses, including many other positive-strand RNA viruses from other families. Understanding how these viruses replicate and targeting key points in their life cycle can help advance antiviral treatments worldwide.

BMV has a genome that is divided into three 5' capped RNAs. RNA1 (3.2 kb) encodes a protein called 1a (109 kDa), which contains both an N-proximal methyltransferase domain and a C-proximal helicase-like domain. The methyltransferase domain shows sequence similarity to other alphavirus m7G methyltransferases and guanyltransferases, called nsP1 proteins, involved in RNA capping. RNA2 (2.9 kb) encodes the 2a protein (94 kDa), the RNA-dependent RNA polymerase, responsible for replication of the viral genome. The dicistronic RNA3 (2.1 kb) encodes for two proteins, the 3a protein (involved in cell-to-cell migration during infection) and the coat protein (for RNA encapsidation and vascular spread), which is expressed from a subgenomic replication intermediate mRNA, called RNA4 (0.9 kb). 3a and coat protein are essential for systemic infection in plants but not RNA replication.Hosts, Symptoms:

BMV commonly infects Bromus inermis (see Bromus) and other grasses, can be found almost anywhere wheat is grown It is also one of the few grass viruses that infects dicotyledonous plants, such as soybean ; however, it primarily infects monocotyledonous plants, such as barley and others in the family Gramineae. The diagnostic species of this disease is maize, where seedlings show a variety of symptoms of this diseases, ( It’s propagation species is barley, which displays a mild mosaic. The assay species of this disease is Chenopodium Hybridum, ( The symptoms of BMV is are similar to most mosaic viruses. The symptoms consist of stunted growth, lesions, mosaic leaves, and death, ( These symptoms generally appear around 10 days after germination of the host plant. The symptoms of this disease affect maize and barley plants the most.

In 2015, it was found that BMV had coinfected Triticale with Wheat Streak Mosaic Virus. This was the first report of coinfection between those two viruses and raises and the first report of BMV infecting Triticale. This raises questions on whether or not the two viruses share a common vector and how they interact with each other. They are currently researching further into this occurrence (K. Trzmiel, 2015).


As of now there is no treatment for this virus once the plant has been infected. There are only measures of prevention of this disease. One option is to use a strain of plant that is resistant to this virus. Since this is a virus fungicides will have no effect on the spread or infection of this disease. Make sure to remove all perennial weeds in the area and to use insecticide to help kill vectors of this disease, ( Make sure to clean equipment and hands before contact with plants. Lastly, removal of infected plants is crucial to the health of surrounding plants and is key to stopping the spread of this disease, (Wheat Streak Mosaic Virus on Wheat: Biology and Management). There are currently no biological control methods to combat this virus. It has been found that the most effective way to combat this virus is to use strains of crop that have resistance to this virus and to use pesticides to remove any vectors that could carry this disease because one of the number one causes of this disease vectors transmitting it to multiple plants after taking up the virus.

Environment, Importance:

Environments that are most suitable for this disease are generally damp due the fact that viruses are transmitted easier when the plants are wet. It is also found in areas that have a heavy amount of wheat plants present and where there is a lot of human contact or exposure Humans are one of the most common vectors used to spread this disease. The temperature range at which this disease is most infective at 20°C to 36°C, according to “Plant Viruses” on page 417. There are multiple vectors for this virus. The vector that is most associated with this disease is the Oulema melanopus L. beetle, ( This beetle is found over a large portion of the Midwest and is one of the biggest carriers of this pathogen.The importance of this disease is it can severely reduce yield of the host plants and the fact it has a wide variety of host plants that it infects. In as study performed in Ohio, they found that the BMV can reduce yield by as much as 61% in soft red winter wheat. The findings found in the Ohio study suggest that Brome Mosaic Virus might have a greater impact on wheat production than previously thought (Hodge, 2018). Farmers have to take great measures to prevent and contain this virus in order to ensure that they produce a quality crop with maximum yield, (Stabilization of Brome Mosaic Virus, page 99-101).

Eastern equine encephalitis

Eastern equine encephalitis (EEE), commonly called Triple E or, sleeping sickness (not to be confused with trypanosomiasis) is a zoonotic alphavirus and arbovirus present in North, Central, and South America and the Caribbean. EEE was first recognized in Massachusetts, United States, in 1831 when 75 horses died mysteriously of viral encephalitis.

Epizootics in horses have continued to occur regularly in the United States. It can also be identified in asses and zebras. Due to the rarity of the disease, its occurrence can cause economic impact in relation to the loss of horses and poultry. EEE is found today in the eastern part of the United States and is often associated with coastal plains. It can most commonly be found in East and Gulf coast states. In Florida, about one to two human cases are reported a year, although over 60 cases of equine encephalitis are reported. Some years in which conditions are favorable for the disease, the number of equine cases is over 200. Diagnosing equine encephalitis is challenging because many of the symptoms are shared with other illnesses and patients can be asymptomatic. Confirmations may require a sample of cerebral spinal fluid or brain tissue, although CT scans and MRI scans are used to detect encephalitis. This could be an indication that the need to test for EEE is necessary. If a biopsy of the cerebral spinal fluid is taken, it is sent to a specialized laboratory for testing.EEEV is closely related to Venezuelan equine encephalitis virus and western equine encephalitis virus.

Eilat virus

The Eilat virus (EILV) is a unique Alphavirus which is known mainly for its host range restriction generally to insects (primarily to mosquitoes) by means of RNA replication. This exclusive virion (a thorough virus which is made of an RNA or DNA core with a protein coat), is found in the Negev desert. It is incapable of infecting vertebrate cells, differentiating it from the series of mosquitoes-borne alphaviruses.

Everglades virus

Everglades virus (EVEV) is an alphavirus included in the Venezuelan equine encephalitis virus complex. The virus circulates among rodents and vector mosquitoes and sometimes infects humans, causing a febrile illness with occasional neurological manifestations. The virus is named after the Everglades, a region of subtropical wetlands in southern Florida. The virus is endemic to the U.S. state of Florida, where its geographic range mirrors that of the mosquito species Culex cedecei. Most clinical cases of infection occur in and around the city of Miami.

Getah virus

The Getah virus is a mosquito-borne arbovirus in the Alphavirus genus. The virus was first isolated in Malaysia in 1955 from the Culex gelidus mosquito. It has been known to infect pigs but more commonly affects horses. The virus was isolated near rubber plantations; the word Getah means rubber in Malay. The first outbreak among racehorses occurred in Japan September–November 1978. The Getah virus is widely distributed in the countries of South-east Asian and in Northern Australia.

Global Vaccines

Global Vaccines, Inc is a non-profit company set up to design and develop affordable vaccines for people in poor countries.

Highlands J virus

The Highlands J (HJ) virus is a zoonotic alphavirus native to North and South America. It maintains a natural reservoir in the songbird population of freshwater swamps (generally scrub jays and blue jays) and is transmitted by the bite of the female Culiseta melanura mosquito.

Though nearly identical in structure and natural cycle to the Eastern equine encephalitis virus, it is considerably less virulent than its cousin, causing relatively mild symptoms in its primary avian reservoir and only nominally capable of transmission to mammals. A 1995 study conducted in Florida swampland found that 15% of swamp-dwelling jays tested positive for HJ antibodies, all of which were asymptomatic and in apparent good health. Recorded bird deaths from HJ infection are uncommon but not rare, and include several domestic turkeys at a commercial facility and young broiler chickens in an experimental setting.

Transmission to equines or humans via mosquito is also possible, though even more rare. During the 1990-1991 St. Louis encephalitis outbreak in Missouri, 4 patients were found to be comorbidly infected with SLE and HJ, though no harmful effects were attributed to the HJ alone. A limited survey of swamp-dwelling rodents in Florida found one cotton mouse and one cotton rat with antibodies to HJ, both asymptomatic. The sole mammalian fatality attributed to HJ was a Florida horse originally diagnosed with Western equine encephalitis in 1964, which was later redetermined in 1989 to have been caused by HJ.Despite its negligible virulence in humans, it is often tested for in US domestic mosquito control programs as an indicator of fruitful conditions for other mosquito-borne zoonoses to multiply.

Mayaro virus disease

Mayaro virus disease is a mosquito-borne zoonotic pathogen endemic to certain humid forests of tropical South America. Infection with Mayaro virus causes an acute, self-limited dengue-like illness of 3–5 days' duration. The causative virus, abbreviated MAYV, is in the family Togaviridae, and genus Alphavirus. It is closely related to other alphaviruses that produce a dengue-like illness accompanied by long-lasting arthralgia. It is only known to circulate in tropical South America.

Middelburg virus

Middelburg virus (MIDV) is an Alphavirus of the Old World Group that has likely endemic and zoonotic potential... It is of the viral family Togaviridae. It was isolated from mosquitos in 1957 in South Africa, MDIV antigens have now been found in livestock, horses, and humans [1].

Pogosta disease

Pogosta disease is a viral disease. The symptoms of the disease include usually rash, as well as mild fever and other flu-like symptoms; in most cases the symptoms last less than 5 days. However, in some cases, the patients develop a painful arthritis. There are no known chemical agents available to treat the disease.It has long been suspected that the disease is caused by a Sindbis-like virus, a positive-stranded RNA virus belonging to the Alphavirus genus and family Togaviridae. In 2002 a strain of Sindbis was isolated from patients during an outbreak of the Pogosta disease in Finland, confirming the hypothesis.This disease is mainly found in the Eastern parts of Finland; a typical Pogosta disease patient is a middle-aged person who has been infected through a mosquito bite while picking berries in the autumn. The prevalence of the disease is about 100 diagnosed cases every year, with larger outbreaks occurring in 7-year intervals.


Polyarthritis is any type of arthritis that involves 5 or more joints simultaneously. It is usually associated with autoimmune conditions and may be experienced at any age and is not sex specific.

Ross River virus

Ross River virus (RRV) is a small encapsulated single-strand RNA Alphavirus endemic to Australia, Papua New Guinea and other islands in the South Pacific. It is responsible for a type of mosquito-borne non-lethal but debilitating tropical disease known as Ross River fever, previously termed "epidemic polyarthritis". The virus is suspected to be enzootic in populations of various native Australian mammals, and has been found on occasion in horses.

Semliki Forest virus

The Semliki Forest virus was first isolated from mosquitoes in the Semliki Forest, Uganda by the Uganda Virus Research Institute in 1942 and described by Smithburn & Haddow. It is known to cause disease in animals including humans. It is an Alphavirus found in central, eastern, and southern Africa.

The Semliki Forest virus is a positive-stranded RNA virus with a genome of approximately 13,000 base pairs which encodes nine proteins. The 5’ two thirds of the genome encode four non-structural proteins concerned with RNA synthesis and the structural proteins are encoded in the 3’ third. Of the structural proteins, the C proteins makes 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, 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 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 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, and as a tool in gene therapy.Since Semliki Forest virus naturally infects cells of the central nervous system it has been pre-clinically tested as an oncolytic virus against the severe brain tumour type glioblastoma. The SFV 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. The modified virus was also found to efficiently kill human glioblastoma tumour cell lines.

Sindbis virus

Sindbis virus (SINV) is a member of the Togaviridae family, in the alphavirus subfamily. The virus was first isolated in 1952 in Cairo, Egypt. The virus is transmitted by mosquitoes (Culex spp.) SINV causes sindbis fever in humans and the symptoms include arthralgia, rash and malaise. Sindbis fever is most common in South and East Africa, Egypt, Israel, Philippines and parts of Australia. Sindbis virus is an "arbovirus" (arthropod-borne) and is maintained in nature by transmission between vertebrate (bird) hosts and invertebrate (mosquito) vectors. Humans are infected with Sindbis virus when bitten by an infected mosquito. SINV has been linked to Pogosta disease in Finland, Ockelbo disease in Sweden and Karelian fever in Russia.


Togaviridae is a family of viruses. Humans, mammals, birds, and mosquitoes serve as natural hosts. There are currently 31 species in this family in a single genus. Diseases associated with alphaviruses include arthritis and encephalitis.

Togavirus 5' plus strand cis-regulatory element

The Togavirus 5' plus strand cis-regulatory element is an RNA element which is thought to be essential for both plus and minus strand RNA synthesis.Genus Alphavirus belongs to the family Togaviridae. Alpha viruses contain secondary structural motifs in the 5' UTR that allow them to avoid detection by IFIT1.See also

Rubella virus 3' cis-acting element

Western equine encephalitis virus

The Western equine encephalomyelitis virus is the causative agent of relatively uncommon viral disease Western equine encephalomyelitis (WEE). An Alphavirus of the family Togaviridae, the WEE virus is an arbovirus (arthropod-borne virus) transmitted by mosquitoes of the genera Culex and Culiseta. WEE is a recombinant virus between two other alphaviruses, an ancestral Sindbis virus-like virus, and an ancestral Eastern equine encephalitis virus-like virus. There have been under 700 confirmed cases in the U.S. since 1964. This virus contains an envelope that is made up of glycoproteins and nucleic acids. The virus is transmitted to people and horses by bites from infected mosquitoes (Culex tarsalis) and birds during wet, summer months.In the U.S. WEE is seen primarily in states and Canadian provinces west of the Mississippi River. The disease is also seen in countries of South America. WEE is commonly a subclinical infection; symptomatic infections are uncommon. However, the disease can cause serious sequelae in infants and children. Unlike Eastern equine encephalitis, the overall mortality of WEE is low (approximately 4%) and is associated mostly with infection in the elderly. Approximately 15-20% of horses that acquire the virus will die or be put down. There is no human vaccine for WEE and there are no licensed therapeutic drugs in the U.S. for this infection. According to the CDC, geographic occurrence for this virus is worldwide, and tends to be more prevalent in places in and around swampy areas where human populations tend to be limited. The virus affects the brain and spinal cord of the infected host.

Available protein structures:
Pfam  structures / ECOD  
PDBsumstructure summary
Available protein structures:
Pfam  structures / ECOD  
PDBsumstructure summary
Available protein structures:
Pfam  structures / ECOD  
PDBsumstructure summary


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