A diagnosis of motor Parkinson’s disease (PD) is preceded by a prolonged premotor phase with accumulating neuronal damage. Here we examined the temporal relation between α-synuclein (α-syn) T cell reactivity and PD. A longitudinal case study revealed that elevated α-syn-specific T cell responses were detected prior to the diagnosis of motor PD, and declined after. The relationship between T cell reactivity and early PD in two independent cohorts showed that α-syn-specific T cell responses were highest shortly after diagnosis of motor PD and then decreased. Additional analysis revealed significant association of α-syn-specific T cell responses with age and lower levodopa equivalent dose. These results confirm the presence of α-syn-reactive T cells in PD and show that they are most abundant immediately after diagnosis of motor PD. These cells may be present years before the diagnosis of motor PD, suggesting avenues of investigation into PD pathogenesis and potential early diagnosis.

Several innate sensing pathways contribute to the control of early cytomegalovirus (CMV) infection, leading to a multiphasic type I interferon (IFN-IC ytomegalovirus (CMV) (human herpesvirus 5 [HHV-5], a betaherpesvirus) is one of the most common etiological agents of chronic viral infection in humans, with primary infection developing in the majority of people at relatively young ages and lasting for life (1). Although acute CMV infection is mostly asymptomatic in healthy individuals, debilitating and even fatal complications arise in those with weakened immune systems, including pregnant women, infants, transplant recipients, and HIV patients. Remarkably, a recent analysis of monozygotic twin pairs revealed that CMV infection was the primary factor driving nonheritable diversity in the immune system (2). Consistent with the dramatic impact of CMV on the host immune system, infection has been associated with multiple chronic inflammatory conditions, including high blood pressure, heart disease/atherosclerosis, cancer, and aging-related immunodeficiencies (3, 4). Despite the clinical importance of human CMV (HCMV), there is currently no vaccine, and antiviral drugs are relatively toxic and cannot restrict viral persistence/latency.Both mouse CMV (MCMV) and HCMV contain a linear double-stranded DNA (dsDNA) genome of ϳ230 kb encoding hundreds of viral open reading frames (ORFs) (5, 6). CMV harbors an arsenal of immunoregulatory genes that allow the virus to evade or dampen host immune defenses. However, despite these numerous strategies, the virus still induces significant levels of type I interferon (IFN-I) from infected cells both in vitro and in vivo. We have previously shown that MCMV induces a biphasic IFN-I response in vivo, with the first wave of IFN-I being completely independent of Toll-like receptor (TLR), Nalp3, and MAVS and emanating from virally infected stromal cells during the first 12 h (7,8). This "first burst" of IFN-I is followed by a later wave produced at 36 to 44 h by plasmacytoid dendritic cells (DCs) (pDCs) and conventional DCs (cDCs) in response to viral particles released from the infected stroma (7,(9)(10)(11). It is the first wave of IFN-I that is critical to limit viral spread in the peripheral organs (7), while the second pDC-derived wave is mostly dispensable for restricting MCMV replication levels (12). Despite our previous work showing that lymphotoxin (LT) signaling is required to promote an optimal first-phase IFN-I response to MCMV in vivo (7,8,11,13,14), the specific innate sensing pathway required for this initial production has remained uncharacterized, although

Highlights d ZIKV preferentially infects glioblastoma stem cells (GSCs) rather than neural precursor cells d ZIKV kills SOX2 + cells from a diverse array of malignant brain tumors d SOX2 determines susceptibility to ZIKV infection with reduced antiviral responses d Integrin a v b 5 is a GSC marker and promotes Zika virus infection of GSCs

No abstract

Chikungunya infection is a major disease of public health concern. The recurrent outbreaks of this viral disease and its progressive evolution demands a potential strategy to understand major aspects of its pathogenesis. Unlike other alphaviruses, Chikungunya virus (CHIKV) pathogenesis is poorly understood. In every consecutive outbreak, some new symptoms associated with virulence and disease manifestations are being reported such as neurological implication, increased severity and enhanced vector competence. In order to unravel the mechanism of the disease process, proteomic analysis was performed to evaluate the host response in CHIKV-infected mice tissues. Comparative analysis of the multiple gels representing the particular tissue extract from mock and CHIKV-infected tissues revealed a drastic reprogramming of physiological conditions through 35 and 15 differentially expressed proteins belonging to different classes such as stress, inflammation, apoptosis, urea cycle, energy metabolism, etc. from liver and brain, respectively. Based on the alterations obtained in the CHIKV mouse model, most of the aspects of CHIKV infection such as disease severity, neurological complications, disease susceptibility and immunocompetence could be defined. This is the first report unravelling the complicated pathways involved in the mechanism of Chikungunya disease pathogenesis employing proteomic approach.