Subject(s)
Meningococcal Infections/diagnosis , Meningococcal Infections/microbiology , Neisseria meningitidis/classification , Pericarditis/diagnosis , Pericarditis/microbiology , Adult , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Electrocardiography , Genome, Bacterial , Humans , Italy/epidemiology , Male , Meningococcal Infections/epidemiology , Neisseria meningitidis/drug effects , Neisseria meningitidis/genetics , Neisseria meningitidis/isolation & purification , Pericarditis/epidemiology , Symptom Assessment , Whole Genome SequencingABSTRACT
The etiology of multiple sclerosis (MS) is still unclear. The immuno-pathogenic phenomena leading to neurodegeneration are thought to be triggered by environmental (viral?) factors operating on predisposing genetic backgrounds. Among the proposed co-factors are the Epstein Barr virus (EBV), and the potentially neuropathogenic HERV-W/MSRV/Syncytin-1 endogenous retroviruses. The ascertained links between EBV and MS are history of late primary infection, possibly leading to infectious mononucleosis (IM), and high titers of pre-onset IgG against EBV nuclear antigens (anti-EBNA IgG). During MS, there is no evidence of MS-specific EBV expression, while a continuous expression of HERV-Ws occurs, paralleling disease behaviour. We found repeatedly extracellular HERV-W/MSRV and MSRV-specific mRNA sequences in MS patients (in blood, spinal fluid, and brain samples), and MRSV presence/load strikingly paralleled MS stages and active/remission phases. Aim of the study was to verify whether HERV-W might be activated in vivo, in hospitalized young adults with IM symptoms, that were analyzed with respect to expression of HERV-W/MSRV transcripts and proteins. Healthy controls were either EBV-negative or latently EBV-infected with/without high titers of anti-EBNA-1 IgG. The results show that activation of HERV-W/MSRV occurs in blood mononuclear cells of IM patients (2Log10 increase of MSRV-type env mRNA accumulation with respect to EBV-negative controls). When healthy controls are stratified for previous EBV infection (high and low, or no anti-EBNA-1 IgG titers), a direct correlation occurs with MSRV mRNA accumulation. Flow cytometry data show increased percentages of cells exposing surface HERV-Wenv protein, that occur differently in specific cell subsets, and in acute disease and past infection. Thus, the data indicate that the two main links between EBV and MS (IM and high anti-EBNA-1-IgG titers) are paralleled by activation of the potentially neuropathogenic HERV-W/MSRV. These novel findings suggest HERV-W/MSRV activation as the missing link between EBV and MS, and may open new avenues of intervention.
Subject(s)
Endogenous Retroviruses/physiology , Herpesvirus 4, Human/physiology , Infectious Mononucleosis/complications , Multiple Sclerosis/virology , Virus Activation , Adolescent , Adult , Case-Control Studies , Female , Humans , Infectious Mononucleosis/virology , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/virology , Male , RNA, Viral/genetics , RNA, Viral/metabolism , Viral Envelope Proteins/genetics , Viral Envelope Proteins/metabolism , Virus Latency , Young AdultABSTRACT
Central nervous system (CNS) symptoms have been reported in clinical trials and case reports in patients receiving raltegravir. We investigated CNS symptoms in 453 HIV-infected patients. Of these 47 (10.4%) developed at least one drug-related CNS symptom. Predictors of CNS symptoms were concomitant therapy with tenofovir or with proton pump inhibitors that can increase raltegravir concentration. Thus, our data suggest a possible correlation between high raltegravir plasma concentrations and CNS symptoms, and therefore their monitoring in clinical practice.
Subject(s)
Anti-HIV Agents/adverse effects , Anti-HIV Agents/blood , Central Nervous System/drug effects , HIV Infections/drug therapy , Pyrrolidinones/adverse effects , Pyrrolidinones/blood , Adenine/adverse effects , Adenine/analogs & derivatives , Adenine/blood , Anti-HIV Agents/administration & dosage , Central Nervous System/physiopathology , Drug Administration Schedule , Drug Interactions , Female , HIV Infections/blood , HIV Infections/physiopathology , Humans , Male , Organophosphonates/adverse effects , Organophosphonates/blood , Pyrrolidinones/administration & dosage , Raltegravir Potassium , Tenofovir , Treatment Outcome , Viral LoadABSTRACT
Mediterranean spotted fever (MSF) is endemic in the Mediterranean area. We carried out a retrospective study to investigate the association between socio-demographic and climatic factors and MSF incidence in northern Sardinia. We found that maximum temperature levels during the previous summer were associated with increases in MSF incidence.
