The asterisk between nsP3 and nsP4 in the NS-ORF indicates the stop codon present in some alphaviruses that must be translationally-read through to produce a precursor containing nsP4. The sequences encompassed by the sgRNA are also shown. Alphavirus replication complexes termed spherules are initially formed at the plasma membrane of infected vertebrate cells Frolova et al.
The initial P polyprotein is cleaved by the viral protease activity of the nsP2 protein into P precursor protein and nsP4; these proteins form the replication complex associated with negative-sense RNA replication Lemm et al. Cleavage of the P polyprotein is highly regulated and generates nsP1, nsP2 and nsP3 individual proteins, which are involved in the synthesis of positive-sense RNA Lemm et al.
Both alphavirus non-structural proteins and RNAs interact with multiple cellular proteins; some of these interactions are essential for replication Sokoloski et al. Figure 3. Model for the processing of the alphavirus nonstructural polyprotein during replication. When low levels of P are present, cis-cleavage of P generates the negative-sense RNA replicase of the virus.
This results in primarily negative-sense RNA being transcribed from the incoming genomic RNA of the virus upper panel. Eventually, replicase complexes capable of producing negative-sense RNA will no longer be present in the infected cell resulting in the complete cessation of negative-sense RNA synthesis lower panel.
The presence of a leaky opal termination codon indicated by an asterisk in the virus genome is believed to lead to a more rapid conversion to the production of positive-sense RNA. Alphavirus structural polyproteins are translated from a subgenomic mRNA. Alphavirus polyproteins are then cleaved by both viral and cellular proteases to produce individual structural proteins Firth et al. The glycoproteins that are produced are inserted into the endoplasmic reticulum during translation and are translocated to the plasma membrane.
Upon generation of a sufficient amount of CP protein, this protein assembles with the viral RNA to form the viral nucleocapsids in the cytosol. Budding through the plasma membrane leads to the acquisition of a lipid envelope containing the two main membrane glycoproteins E1 and E2 Frey , Jose et al.
The Togaviruses - 1st Edition
The alphaviruses were originally described as Group A arboviruses based upon their antigenic cross-relationships. Using specific serological testing, antigenic complexes were proposed where all members of a particular complex were closely related to each other.
Eight eleven including the fish, seal and mosquito-specific alphaviruses such complexes are described whose members, for the most part, are also genetically clustered Kuhn Vertebrate hosts include humans, non-human primates, equids, birds, amphibians, reptiles, rodents, and pigs Kuhn There are two aquatic alphaviruses, southern elephant seal virus and salmon pancreas disease virus, infecting sea mammals and fish respectively. Furthermore, representing a new host-restricted complex within the alphaviruses, Eilat virus EILV , has been shown to only infect insect cells and is incapable of replicating in vertebrate cells Nasar et al.
With a few exceptions, most alphaviruses are transmitted alternately between their vertebrate and invertebrate hosts.
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For many alphaviruses, humans are dead-end hosts, incapable of developing sufficient viremia to infect mosquitoes, although human-mosquito-human transmission has been implicated in chikungunya virus CHIKV outbreaks. The aquatic alphaviruses, which include southern elephant seal virus La Linn et al. The insect-specific Eilat virus is defective for replication in vertebrates, and therefore is probably maintained via vertical transmission in mosquitoes Nasar et al.
The alphaviruses have a worldwide distribution, inhabiting all continents except Antarctica Powers et al. The alphaviruses are geographically restricted based on preferred ecological conditions, reservoir hosts and vector species, but continue to move around the globe and colonize new areas.
Based on their distribution, alphaviruses have classically been described as Old World or New World viruses. Most alphaviruses are cytopathic to vertebrate cells and cause a short febrile illness that can lead to prolonged arthritis or encephalitis, but are rarely fatal. Species demarcation considers a combination of each of the criteria listed above. For example, the justification for Everglades virus remaining as a distinct species is based upon its avirulence for equids, as well as a different rodent host and mosquito vector usage in Southern Florida.
The reason that some very divergent strains such as those of VEEV and Sindbis virus are considered subtypes but not species reflects the lack of phenotypic information. Mosso das Pedras virus: named after isolation locality in Brazil Calisher et al.
Semliki Forest virus: first isolated from Semliki Forest in Uganda. Among alphaviruses, salmon pancreatic disease virus SPDV is the most divergent, with sequence similarity only in parts of the structural and non-structural proteins. However, this may not necessarily mean that this virus is ancestral, but could instead reflect its adaptation to the fish host and a lack of evolutionary constraints for other alphaviruses associated with alternating transmission between a mammalian host and arthropod vector.
An alignment of alphavirus sequences excluding SPDV , demonstrates a high level of heterogeneity in the hypervariable region HVR of the nsP3 gene, the capsid gene, and a few short regions scattered throughout the genome where accurate alignment cannot be made. A phylogenetic tree based on the conserved regions of envelope genes is shown in Figure 4.
Figure 4. The tree is mid-point rooted. Bootstrap values above 70 generated by replicates of neighbour-joining tree are indicated next to the main branches.
The first major clade further diverges into Venezuelan equine encephalitis and eastern equine encephalitis complexes. The second bifurcates into Trocara virus, Eilat virus complex, and western equine encephalitis complex, sequentially. The last one contains Barmah Forest virus, salmon pancreas disease virus, southern elephant seal virus, Ndumu virus, Middleburg virus, and Semliki Forest virus complex.
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To learn more about Copies Direct watch this short online video. Need help? How do I find a book? Can I borrow this item? Can I get a copy? Can I view this online? Ask a librarian. Alphaviruses are predominantly transmitted through the bite of an infected mosquito. Rubella is transmitted through airborne aerosol droplets. Treatment for togavirus infections is generally supportive in order to manage symptoms or complications.
An effective measure in preventing rubella is through childhood immunizations using the MMR Measles, Mumps Rubella vaccine. There are no human vaccines available for the prevention of the alphavirus diseases. Other preventive measures include vector-control and personal protection against mosquito bites. Eastern Equine encephalitis EEE. Western Equine encephalitis WEE.