The Transient Receptor Potential Vanilloid 2 (TRPV2) Channel Facilitates Virus Infection Through the Ca2+ -LRMDA Axis in Myeloid Cells.

The transient receptor potential vanilloid 2 (TRPV2) channel is a nonselective cation channel that has been implicated in multiple sensory processes in the nervous system. Here, it is shown that TRPV2 in myeloid cells facilitates virus penetration by promoting the tension and mobility of cell membrane through the Ca2+ -LRMDA axis. Knockout of TRPV2 in myeloid cells or inhibition of TRPV2 channel activity suppresses viral infection and protects mice from herpes simplex virus 1 (HSV-1) and vesicular stomatitis virus (VSV) infection. Reconstitution of TRPV2 but not the Ca2+ -impermeable mutant TRPV2E572Q into LyZ2-Cre;Trpv2fl/fl bone marrow-derived dendritic cells (BMDCs) restores viral infection. Mechanistically, knockout of TRPV2 in myeloid cells inhibits the tension and mobility of cell membrane and the penetration of viruses, which is restored by reconstitution of TRPV2 but not TRPV2E572Q . In addition, knockout of TRPV2 leads to downregulation of Lrmda in BMDCs and BMDMs, and knockdown of Lrmda significantly downregulates the mobility and tension of cell membrane and inhibits viral infections in Trpv2fl/fl but not LyZ2-Cre;Trpv2fl/fl BMDCs. Consistently, complement of LRMDA into LyZ2-Cre;Trpv2fl/fl BMDCs partially restores the tension and mobility of cell membrane and promotes viral penetration and infection. These findings characterize a previously unknown function of myeloid TRPV2 in facilitating viral infection though the Ca2+ -LRMDA axis.

High exposure to statins decrease the risk of new-onset dementia: A nationwide population-based longitudinal cohort study.

Several studies have shown that statin users have a lower risk of new-onset dementia (NOD) compared nonusers. However, other studies have shown opposite results. In this study, we investigated the association between the use of statins and the development of NOD.This was a longitudinal cohort study using data from claim forms submitted to the Taiwanese Bureau of National Health Insurance. The study included patients with NOD and non-NOD subjects from January 2002 to December 2013. We estimated the hazard ratios (HRs) of NOD associated with statin use, whereas nonuser subjects were used as a reference group.A total of 19,522 NOD cases were identified in 100,610 hyperlipidemic patients during the study period. The risk of NOD, after adjusting for sex, age, comorbidities, and concurrent medication, was lower among statin users than nonusers (HR 0.95, 95% CI [confidence interval] 0.94-0.96; P < .001). The adjusted HRs for NOD were 1.53 (95% CI, 1.45-1.62), 0.63 (95% CI, 0.57-0.71), and 0.34 (95% CI, 0.30-0.38) when the cumulative defined daily doses ranged from 28 to 365, 366 to 730, and more than 730 relative to nonusers, respectively.We concluded that statin use is associated with a decreased NOD risk. The protective effect of statins for NOD seemed to be related to high exposure to statins. This study also highlights that high exposure to statins has a dose-response effect on lowering NOD risk.