Project description:Small RNAs play a critical role in host-pathogen interaction. In insects, for instance, small RNA-mediated silencing or RNA interference (RNAi) represents the main antiviral defense system. However, the antiviral role of RNAi has not been clearly proven in higher vertebrates. On the contrary, it is well established that the cell response relies on the recognition of viral RNAs by host pattern recognition receptors (PRR) to trigger the activation of the interferon pathway. Based on this evidence, we wished to contribute to this research field by identifying and characterizing small non-coding RNAs produced in mammalian cells upon RNA virus infection. We focused on Sindbis virus (SINV), the prototypical arbovirus, which by definition, is able to infect both vertebrate hosts and invertebrate vectors and triggers the interferon pathway or RNAi, respectively.

2013-11-19 | GSE48831 | GEO

Sindbis virus strain:MRE16

Project description:Sindbis virus strain:MRE16 Raw sequence reads

| PRJNA699225 | ENA

Mosquitoborne Sindbis Virus Infection and Long-Term Illness.

Project description:An unexpected human outbreak of the mosquitoborne Sindbis virus occurred in a previously nonendemic area of Sweden. At follow-up, 6-8 months after infection, 39% of patients had chronic arthralgia that affected their daily activities. Vectorborne infections may disseminate rapidly into new areas and cause acute and chronic disease.

| S-EPMC6004841 | biostudies-literature

Placement of the structural proteins in Sindbis virus.

Project description:The structure of the lipid-enveloped Sindbis virus has been determined by fitting atomic resolution crystallographic structures of component proteins into an 11-A resolution cryoelectron microscopy map. The virus has T=4 quasisymmetry elements that are accurately maintained between the external glycoproteins, the transmembrane helical region, and the internal nucleocapsid core. The crystal structure of the E1 glycoprotein was fitted into the cryoelectron microscopy density, in part by using the known carbohydrate positions as restraints. A difference map showed that the E2 glycoprotein was shaped similarly to E1, suggesting a possible common evolutionary origin for these two glycoproteins. The structure shows that the E2 glycoprotein would have to move away from the center of the trimeric spike in order to expose enough viral membrane surface to permit fusion with the cellular membrane during the initial stages of host infection. The well-resolved E1-E2 transmembrane regions form alpha-helical coiled coils that were consistent with T=4 symmetry. The known structure of the capsid protein was fitted into the density corresponding to the nucleocapsid, revising the structure published earlier.

| S-EPMC136788 | biostudies-literature

Cross-species comparative analysis of Dicer proteins during Sindbis virus infection

Project description:The role of RNA silencing as a defense mechanism against viruses remains to be formerly established in mammalian somatic cells. Here, we determined the antiviral properties of human and Drosophila Dicer proteins in a heterologous setup. We expressed human Dicer (hDicer) in Drosophila, and Drosophila Dicer-2 in human cells, and measured the impact on the response to Sindbis virus (SINV) infection. In flies, hDicer presents a low processing activity, but partially rescues a Dcr2 null mutation in flies. Expression of Dicer-2 in HEK293 cells allows the processing of SINV RNA into 21-nt-long small RNAs. Nevertheless, instead of conferring a protective effect against SINV, Dicer-2 expression increases viral replication in HEK293 cells. We present evidence that this effect is due to a competition with the interferon pathway. Our results therefore suggest that adding functionial RNA silencing machinery in IFN-competent differentiated mammalian cells can be detrimental for antiviral defense.

2015-12-28 | GSE62934 | GEO

Sindbis virus polyarthritis outbreak signalled by virus prevalence in the mosquito vectors.

Project description:Polyarthritis and rash caused by Sindbis virus (SINV), was first recognised in northern Europe about 50 years ago and is known as Ockelbo disease in Sweden and Pogosta disease in Finland. This mosquito-borne virus occurs mainly in tropical and sub-tropical countries, and in northern Europe it is suggested to cause regularly reoccurring outbreaks. Here a seven-year cycle of SINV outbreaks has been referred to in scientific papers, although the hypothesis is based solely on reported human cases. In the search for a more objective outbreak signal, we evaluated mosquito abundance and SINV prevalence in vector mosquitoes from an endemic area in central Sweden. Vector mosquitoes collected in the River Dalälven floodplains during the years before, during, and after the hypothesised 2002 outbreak year were assayed for virus on cell culture. Obtained isolates were partially sequenced, and the nucleotide sequences analysed using Bayesian maximum clade credibility and median joining network analysis. Only one SINV strain was recovered in 2001, and 4 strains in 2003, while 15 strains were recovered in 2002 with significantly increased infection rates in both the enzootic and the bridge-vectors. In 2002, the Maximum Likelihood Estimated infection rates were 10.0/1000 in the enzootic vectors Culex torrentium/pipiens, and 0.62/1000 in the bridge-vector Aedes cinereus, compared to 4.9/1000 and 0.0/1000 in 2001 and 0.0/1000 and 0.32/1000 in 2003 Sequence analysis showed that all isolates belonged to the SINV genotype I (SINV-I). The genetic analysis revealed local maintenance of four SINV-I clades in the River Dalälven floodplains over the years. Our findings suggest that increased SINV-I prevalence in vector mosquitoes constitutes the most valuable outbreak marker for further scrutinising the hypothesized seven-year cycle of SINV-I outbreaks and the mechanisms behind.

| S-EPMC6738656 | biostudies-literature

Culex pipiens strain:Sindbis virus

Project description:Culex pipiens strain:Sindbis virus Raw sequence reads

| PRJNA350497 | ENA