Multiple sclerosis (MS) is associated with genetic susceptibility and unknown environmental triggers, possible viral infections, but the specific etiological mechanism that subsequently develops into an inflammatory/autoimmune cascade of events is poorly understood. Recently, genetic variants of 2',5'- oligoadenylate synthetase 1 (OAS1) gene, a critical enzyme involved in innate antivirus response, have been associated with differential enzyme activity and type 1 diabetes in both case-control and family studies. We hypothesized that polymorphisms in the OAS1 gene could influence the susceptibility to MS. To test this hypothesis, we conducted a case-control study of 333 patients with MS and 424 healthy controls and genotyped two OAS1 single nucleotide polymorphisms (SNPs) by restriction fragment length polymorphism method: rs 10774671, A/G SNP altering the splicing site at the seventh exon, and rs 3741981, a nonsynonymous (Ser162Gly) A/G SNP in the third exon. Haplotype but not single-marker analysis revealed an association of the haplotype created by the G allele at rs 10774671 and the A allele at rs 3741981 with the susceptibility to MS (P value = 8.8 x 10(-5)). Subjects carrying this haplotype had an increased risk of MS comparing with those not carrying it (odds ratio = 4.7, 95% confidence interval 2.1-10.9). Our findings indicate that the OAS1 gene polymorphisms may confer susceptibility to MS or serve as markers of functional variants and suggest that OAS1 activity is involved in the etiology of the disease. Future studies in a larger sample and association analysis with functional variants will clarify the role of the OAS1 gene in the susceptibility to MS.

BackgroundThe morphogenesis of herpes simplex virus type 1 (HSV-1) comprises several events, of which some are not completely understood. It has been shown that HSV-1 glycoproteins accumulate in the trans-Golgi network (TGN) and in TGN-derived vesicles. It is also accepted that HSV-1 acquires its final morphology through a secondary envelopment by budding into TGN-derived vesicles coated with viral glycoproteins and tegument proteins. Nevertheless, several aspects of this process remain elusive. The small GTPase Rab27a has been implicated in regulated exocytosis, and it seems to play a key role in certain membrane trafficking events. Rab27a also seems to be required for human cytomegalovirus assembly. However, despite the involvement of various Rab GTPases in HSV-1 envelopment, there is, to date, no data reported on the role of Rab27a in HSV-1 infection.ResultsHerein, we show that Rab27a colocalized with GHSV-UL46, a tegument-tagged green fluorescent protein-HSV-1, in the TGN. In fact, this small GTPase colocalized with viral glycoproteins gH and gD in that compartment. Functional analysis through Rab27a depletion showed a significant decrease in the number of infected cells and viral production in Rab27a-silenced cells.ConclusionsAltogether, our results indicate that Rab27a plays an important role in HSV-1 infection of oligodendrocytic cells.

The human promonocytic U937 cell line, which is moderately susceptible to poliovirus infection, has been used to investigate the induction of apoptosis by this virus. Infection of U937 cells with poliovirus induces morphological changes typical of apoptosis. Poliovirus-resistant U937 cells (PRU) have been isolated that are resistant to apoptosis induced by poliovirus, but that undergo apoptosis after treatment with TNF plus cycloheximide. Despite the fact that poliovirus triggers nitric oxide production in U937 cells, the inhibitor of inducible nitric oxide (NO) synthase, N(omega)-monomethyl-l-arginine, did not hinder apoptosis after infection, suggesting that NO does not play a direct role in this process. Finally, poliovirus infection of U937 cells led to the cleavage of pro-caspase-3 and poly(ADP-ribose)polymerase, indicating the activation of the CPP32 ICE-like cysteine protease in the induction of apoptosis. Our findings suggest that cellular death takes place in U937 cells productively infected by poliovirus as a result of apoptosis and involves caspase activation.