Sindbis Virus
1. Classification
Sindbis virus is a species that occupies human, invertebrate and vertebrate hosts (1).
Domain: Viruses; Realm: Riboviria; Kingdom: Orthornavirae; Phylum: Kitrinoviricota; Class: Alsuviricetes; Order: Martellivirales; Family: Togaviridae; Genus: Alphavirus
2. Introduction
Sindbis virus (SINV) is a disease-causing RNA virus transferred from animals to humans that is most often observed in Northern Europe and South Africa (2). The clinical infection of SINV is known as Pogosta disease in Finland, Ockelbo disease in Sweden, and Karelian fever in Russia. Symptoms of infection include joint pain, rash, fever, and myalgia; in many patients, these symptoms can continue for months or years and become debilitating (2). After diagnosis, there is no specific treatment available but pain management is typically used to alleviate symptoms through anti-inflammatory drugs (2). Potential cancer therapies have been developed using a viral vector of SINV to introduce specific genomic information into a host cell (3). However, it is unknown whether SINV vectors are effective in a clinical setting outside of a lab (2). It is also not yet well understood how host cells signal and respond to infection of SINV (2). Current research is focused on understanding the pathophysiology of SINV so that effective prevention and treatment methods for the virus can be developed (3), as well as expanding the phylogenetic tree of different SINV strains (4).
3. Genome structure
The genome of SINV is a single-stranded positive sense RNA molecule (4). Among the 44 strains that have been sequenced, the genome ranges from 11-12 kilobases and is additionally capped at the 5' end and polyadenylated at the 3' end (4, 5, 6). The highest variance between SINV strains at the amino acid level was 22.2% and currently breaks down into 5 genotypic groups: SIN-I (Europe and Africa), SIN-II (Australia), SIN-III (East Asia), SIN-IV (Azerbaijan and China), and SIN-V (New Zealand) (7). The viral genome encodes mRNA for five structural proteins and four nonstructural proteins (2). The small plaque, heat resistant strain of SINV has a genome that is 11,703 nucleotides long. The genome has 59 nucleotides of 5' untranslated regions from the 5’ cap (4). Following the 5’ untranslated region are 7539 nucleotides of open reading frame that encode nonstructural polypeptides (nsPs), nsP1, nsP2, nsP3, and nsP4, which are involved in transcription and translation of the viral genome (4). Two different polyprotein precursors can be produced from this part of the genome, either P123 or P1234 (Figure 1) (4, 8). The nonstructural proteins then work in the replication complex to create complementary RNAs in the process of viral genome replication (8, 9). Following the first open reading frame are 48 untranslated nucleotides located between the sequence encoding the nonstructural proteins and the structural proteins (4). After the 48 untranslated nucleotides, the next 3735 nucleotides of the open reading frame encode structural proteins which are translated to a polypeptide precursor from the mRNA (4). This precursor is then processed through protein breakdown into the nucleocapsid protein, two integral membrane glycoproteins, and two small peptides (the last two are not found in the mature virus particle). These proteins are named capsid, E1 and E2, and E3 and 6K, respectively (4, 10). Found at the end are 322 nucleotides of the 3' untranslated region (4).
4. Replication
SINV uses receptor-mediated endocytosis to enter host cells through clathrin-coated vesicles (2, 4, 5). However, recent research has indicated that the genome of SINV may also enter directly through pores formed at the host cell membrane (1). The first step in the replication of the viral genome is the translation of the viral mRNA, allowing the nonstructural proteins to be expressed (10). The nonstructural proteins then assemble with host factors and become the replication complex (8, 9). The replication complex replicates the viral mRNA and produces the complementary negative sense strand RNAs (9). Using the negative strand as a template, new positive RNA strands are made by the replication complex and are eventually incorporated into new viral particles (9, 10). To create new viral particles, the E1 and E2 glycoproteins, two of the structural proteins, get translated into transmembrane proteins of the host cell (10). After folding, the two proteins form heterodimers and sugars are added via glycosylation in the Golgi apparatus. Following this post-translational modification, the dimer is transported to the plasma membrane of the host cell and undergoes further organization into spikes by assembling with two other dimers to become a trimeric spike (10). 80 of these spikes assemble to form an icosahedral structure around the virus (10). While the viral proteins are being assembled, nucleocapsid cores are formed in the cytoplasm of host cells (10). The nucleocapsid cores are transported to the plasma membrane of the cell where they interact with the cytoplasmic domains of the E1-E2 trimers. When viral particles are ready to leave the host cell, the host cell membrane starts to bud (10). In this budding process, the glycoproteins and the plasma membrane form a viral envelope in the aforementioned icosahedral structure. The capsid, E1, and E2 proteins compose the mature virus in combination with a host cell-derived membrane (8, 10, Figure 2). The new particle can then continue to infect other host cells (10). Heparan sulfate, a carbohydrate chain expressed on the surface of animal cells, participates in the binding of SINV to host cells (12). The amount of heparan sulfate present is a crucial factor that determines how strongly the virus can bind to host cells (12). When the virus is bound to heparan sulfate, it can then enter and replicate inside the host cell (12).
5. Particle structure
SINV is an enveloped virus, meaning the virus is wrapped in a coat of the host cell’s plasma membrane (10). This membrane holds 80 spike proteins, each composed of 3 heterodimers, where each heterodimer consists of a pair of E1 and E2 glycoproteins (peptide chains with carbohydrate groups attached) (10). It is a spherical virus about 70 nanometers in diameter that contains an icosahedral, or 20-sided, capsid (Figure 2).
5. Metabolic processes
Describe important sources of energy, electrons, and carbon (i.e. trophy) for the organism/organisms you are focusing on, as well as important molecules it/they synthesize(s).
6. Ecology
Habitat; symbiosis; contributions to the environment.
7. Pathology
How does this organism cause disease? Human, animal, plant hosts? Virulence factors, as well as patient symptoms.
8. Current Research
Include information about how this microbe (or related microbes) are currently being studied and for what purpose
9. References
It is required that you add at least five primary research articles (in same format as the sample reference below) that corresponds to the info that you added to this page. [Sample reference] Faller, A., and Schleifer, K. "Modified Oxidase and Benzidine Tests for Separation of Staphylococci from Micrococci". Journal of Clinical Microbiology. 1981. Volume 13. p. 1031-1035.
