Sindbis virus (SINV) is a member of the Alphavirus genus and was first isolated in Egypt in 1952. It is mainly found in wild bird populations and possibly some mammals. Vectors of Sindbis virus include Culex and Culiseta spp. mosquitoes. Sindbis virus is one of the most widespread mosquito-borne viruses in the world, found in Africa, Europe, Asia, and Australia. Illness in humans is usually mild and characterized by acute fever with arthralgia, muscle pain, and rash. Finland has periodic epidemics, where it is called Podosta disease.
Sindbis virus antiviral research and development can be conducted at Biosafety Level -2 (BSL-2). The most common method for identifying Sindbis virus infection is serological assays. Most laboratories rely on hemagglutination inhibition (HI) assay for detecting antibodies, which does not distinguish between IgG and IgM antibodies and therefore cannot distinguish between recent and previous infections. The development of ELISA and immunofluorescent assays will help to differentiate between IgG and IgM antibodies responses. Few articles have been published on the kinetics of antibody responses in Sindbis virus-infected patients. In-house serological assays, such as ELISA, have been established to detect IgG and IgM antibodies to Sindbis virus.
Figure 1. Schematic diagram of alphavirus entry pathway and inhibitors targeting each step.
Sindbis virus is a spherical (T=4) virus with a diameter of 70 nm. It has an icosahedral capsid of 240 monomers and a host cell-derived lipid membrane with 80 trimeric spikes consisting of three heterodimers of E1 and E2 glycoproteins. The positive single-stranded RNA genome size is 11.7kB, with two open reading frames encoding mRNA for four non-structural proteins (NSP1-4) and five structural proteins (C, E3, E2, 6K, and E1) in different replicons, respectively. Sindbis virus enters target cells via a receptor-mediated manner in clathrin-coated vesicles. The translation and assembly of the nucleocapsid take place free in the cytosol, while the replication of RNA requires a specific membranous replication complex. Assembly of virions is accomplished at the plasma membrane where lipid membranes and glycoprotein complexes are obtained (Figure 1). Sindbis virus infection induces type I IFN production in a RIG-I, MDA5 or PKR-dependent manner. Type I IFN plays an important role in controlling Sindbis virus infection, as the lack of its signaling causes the otherwise innocuous virus to gain the ability to propagate, disseminate, and become rapidly fatal. Several IFN-stimulated genes have been reported to act as antiviral factors against Sindbis virus.
There is currently no specific treatment for Sindbis virus infection, and current efforts are focused on pain alleviation using non-steroidal anti-inflammatory drugs. In addition, there is currently no vaccine available to prevent Sindbis virus infection. Mosquito bites are the single most important risk factor for acquiring Sindbis virus infection, so choosing protective clothing to avoid mosquito bites is the first choice to prevent infection. Creative Diagnostics supports clients in Sindbis virus antiviral research and development with extensive knowledge.
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