Journal of NeuroVirology最新文献

Aging people with HIV (PWH) may be at heightened risk of Mild Cognitive Impairment (MCI), including the subtypes amnestic MCI (aMCI) and non-amnestic MCI (naMCI). We examined associations between putative risk factors (HIV clinical variables, lifetime substance exposure, APOE genotype) and clinician consensus-defined MCI status in older PWH. Additionally, we evaluated agreement between clinician consensus aMCI and algorithmic (Jak-Bondi) aMCI classification, as well as overlap between aMCI and HIV-Associated Neurocognitive Disorder (HAND). PWH (N = 56; median age 63; IQR 61-67) completed a neurocognitive battery. Two neuropsychologists assigned consensus diagnoses (aMCI/naMCI/no MCI). Alcohol, cocaine, opioid, and cannabis exposure, years since HIV diagnosis, and time from diagnosis to care were assessed by self-report. APOE was genotyped from whole blood. HIV viral load (detectable/undetectable) was assayed from plasma. Algorithmic aMCI classification was made using modified Jak-Bondi criteria and HAND classification using Frascati criteria. 36% of participants (N = 20) met consensus aMCI criteria. aMCI status was significantly associated with years since HIV diagnosis, time to care, and opioid exposure in age-adjusted models. However, MCI status was not associated with alcohol, cocaine, or cannabis exposure, APOE genotype, or detectable viral load. Agreement between clinician consensus and algorithmic aMCI classification was substantial. Participants with aMCI and naMCI (vs. no MCI) were significantly more likely to meet HAND criteria. Because time since diagnosis and time from diagnosis to care were associated with amnestic MCI in PWH, greater cumulative HIV exposure may be linked to greater neuropathology in aging.

JC polyomavirus (JCPyV) is associated with progressive multifocal leukoencephalopathy (PML), but its plausible role in brain cancers is also disputed. One candidate to mediate cell transformation is the Large T antigen (LTAg), which has the capability to bind the Wnt pathway protein β-catenin, thus deregulating the cell cycle. In the current study, we investigated the presence and molecular state of JCPyV in pediatric brain tumors and the effects of virus-positivity on the Wnt pathway. JCPyV DNA was found in 31/101 (30.7%) brain tumors with a viral load of 3.2 copies/cell. The amplified NCCR revealed an archetype sequence, and VP1 reported a high degree of homology with the reference strain. The LTAg gene was reported in all JCPyV-positive tumors. Interestingly, among them, 5 tissues did not express VP1 and viral miRNAs, supporting a hampering of late region transcription. Over-expression of β-catenin, c-myc and cyclin D1 was observed in JCPyV-positive tissues compared to negative ones, suggesting that the virus may exploit this signaling pathway, potentially contributing to brain carcinogenesis. The current study adds further evidence of JCPyV prevalence in human brain tumors and reports alterations of the Wnt pathway, laying the basis for further investigation on JCPyV-mediated oncogenesis in the brain.

Sleep disturbances are frequently reported in persons with HIV and have been associated with the use of certain integrase strand transfer inhibitors (INSTIs), such as dolutegravir. This exploratory study assessed changes in cerebral function parameters in individuals with insomnia switching INSTIs. Individuals with an insomnia severity index (ISI) above 8 and virologically suppressed on a dolutegravir-containing ART regimen (DTG-ART) were randomised 1:1 to either continue DTG-ART or switch to bictegravir/emtricitabine/tenofovir alafenamide (BIC-ART) for 120 days. Cerebral function parameters were measured longitudinally at baseline (D0) and day 120 (D120) and included: (1) patient-reported outcomes (PROs) assessing sleep, quality of life (QoL) and symptoms related to ART, (2) resting-state functional cerebral MRI (fMRI), examining functional connectivity networks previously associated with DTG use or sleep and (3) plasma soluble inflammatory biomarkers associated with neuroinflammation or HIV disease progression (Neopterin, CXCL10 and IL-6). Functional connectivity analyses were performed using Seed-Based Correlations (SBC), and correlations between connectivity changes, PRO measures and biomarker concentrations determined. Of 19 individuals (12 DTG-ART, 7 BIC-ART), median age was 55 years (range 28-83), all were male and 17 of white ethnicity. Over 120 days, improvements in sleep and QoL in those randomised to BIC-ART vs. DTG-ART were observed. Median change in Insomnia Severity Index (ISI) score - 9 (-14 to -2) vs. -1 (-10 to -4), p = 0.030, Epworth Sleepiness Scale (ESS) -3.0 (-6 to -1) vs. 2 (-3 to 6), p = 0.007 and Short Form-36 Physical Function (SF36-PF) -5 (-40 to 5) vs. 0 (-5 to 15), p = 0.026) for BIC- vs. DTG- ART, respectively. BIC-ART was also associated with increased functional connectivity in the Default Mode and Salience Networks (both p < 0.05), which correlated with improvements in PRO measures (ESS and SF36-PF, both p < 0.05). No significant changes in soluble biomarkers were observed. Individuals with insomnia switching to BIC-ART had improvements in self-reported sleep, QoL and resting state fMRI networks associated with sleep, when compared to those continued on DTG-ART.

The bat-borne Nipah virus, known for causing high mortality rates in humans, has been reported in India (Megaderma spasma), Bangladesh (Pteropus medius), and Malaysia (Pteropus vampyrus) with different bat species serving as reservoirs. The virus also infects various animals, which often act as intermediate hosts in the transmission to humans. Due to the high fatality rates associated with Nipah virus outbreaks, the World Health Organization has flagged it as a significant public health concern, prompting extensive research into the development of antiviral therapeutics and vaccines. However, no effective vaccine or therapeutic agent has yet been established. In this context, we propose a miRNA-based approach to identify key human cellular miRNAs capable of binding to and potentially cleaving or degrading Nipah virus genes implicated in human infections. Our study revealed a substantial number of miRNA binding sites across various viral genes, suggesting a potential mechanism for gene silencing. Furthermore, the calculated free energy values (< 4 kcal/mol) for all three regions; downstream, upstream and target indicate that the thermodynamically favorable binding could facilitate effective miRNA-mediated repressions of viral gene expression. Additionally, the translational efficiency and COSM values suggested swift miRNA-mediated cleavage or degradation of the viral genes. Moreover, analysis of the miRNA-mRNA duplex free energy and secondary structures, as predicted by RNAFold, indicated that the interactions between human miRNAs and Nipah virus genes were thermodynamically stable. These stable duplex formations support the potential for efficient binding, leading to effective gene silencing through cleavage or degradation mechanisms.

Acute encephalitis syndrome (AES) is now being used for surveillance in all encephalitis endemic zones irrespective of the etiology. Numerous viral pathogens possess the ability to invade the CNS and produce neurologic dysfunction. We performed a hospital-based descriptive study between January 2019 to January 2020 in the Department of Microbiology, GMC, Thiruvananthapuram taking samples from 193 AES patients admitted under the Departments of Internal Medicine, Neurology & Paediatrics. The samples were proceeded with PCR/ELISA depending on the clinical history. A viral etiology was established in 48 cases (24.9%) & most were caused by EBV (5.7%). MRI revealed temporal lobe involvement in 9 patients. 20% cases had post-encephalitic sequelae-focal neurological deficits and persistent seizures. Most number of patients were found to have infected with Epstein- Barr virus. Identification of the causative agent is of great importance in AES, as rapid detection and confirmation of etiological agent will have a tremendous impact on the management of outbreaks as well as patient's disease.

Several viral, bacterial, fungal, and protozoan parasite pathogens are capable of causing either active and/or latent chronic infections, particularly if they are highly immuno-evasive. The nine human herpesviruses are among the most evasive pathogens. They can remain latent for decades, but can periodically reactivate into active chronic infections after various triggers: medical treatments causing intentional or unintentional immune system suppression, other pathogen infections, malnutrition, stress, or unusual host cell signaling. Various neurological disorders including dementias and severe autoimmune diseases have been linked to highly prevalent human herpesvirus infections including herpes simplex type 1 and 2, varicella-zoster virus, Epstein-Barr virus, human cytomegalovirus, and herpesviruses 6A, 6B, 7 and 8. For example, dementias including Alzheimer's disease have been extensively linked to herpes simplex type 1 and 2, and herpesvirus 6A and 7, but other herpesviruses may be indirectly involved in dementias. For instance, recent evidence strongly suggests dementias can result from reactivated varicella-zoster herpes virus infections, whereas effective vaccinations against varicella-zoster herpes virus reactivations to avoid shingles have also shown significant reductions in dementia probabilities for vaccinated individuals. This raises questions about how various herpesviruses can initiate or enable neurological diseases including dementias and autoimmune diseases, and how their infections and particularly their reactivations from latency can initiate these diseases.

Mitochondrial DNA (mtDNA) in extracellular vesicles (EVs) may track HIV-related neuronal injury. We measured mtDNA copy number in neuron-derived EVs (NEVs) and total plasma EVs from 48 African American adults stratified by sex, HIV status, and smoking. NEV-mtDNA differed by group (p < 0.05): men with HIV showed the highest levels, markedly exceeding HIV-negative men and all women, while smoking raised NEV-mtDNA only in men. Plasma EV-mtDNA paralleled NEVs but was ~ 100-fold higher, reflecting systemic release. These sex-specific increases implicate HIV as a stronger mitochondrial stressor in men and support NEV-mtDNA as a convenient biomarker of neuro-mitochondrial dysfunction.

Schizophrenia is a complex psychiatric disorder with multifactorial etiologies, including genetic components. The role of Human endogenous retroviruses has been suggested in schizophrenia pathogenesis. This study aims to identify and analyze the shared genetic components between schizophrenia and Human endogenous retroviruses through bioinformatics approaches. Genes associated with schizophrenia and Human endogenous retroviruses were identified and analyzed for overlap. A protein-protein interaction network was constructed, followed by hub gene selection using various algorithms. Functional enrichment analyses were conducted to determine biological processes and pathways involved. Transcription factors and miRNA networks were built to investigate gene regulation. Drug and chemical interactions were examined, and gene-disease associations were assessed. Also, gene expression levels in different brain regions and brain and blood cells were analyzed. Logistic regression analysis was done to evaluate the association of hub genes with schizophrenia. A total of 345 genes were found common between schizophrenia and Human endogenous retroviruses. Six hub genes (AKT1, CD4, CD8A, IL6, STAT1, and TNF) were identified. Gene ontology and pathway analyses indicated immune system involvement. Gene expression analysis showed differential expression patterns in blood and brain cells. IL6 and TNF were significantly upregulated in schizophrenia patients, while AKT1 exhibited downregulation. Logistic regression revealed IL6 and TNF as risk factors, whereas AKT1 showed protective effects. This study found key genetic interactions between schizophrenia and endogenous human retroviruses, with hub genes playing significant roles in immune signaling and neuroinflammation. These findings introduce potential targets for therapeutic interventions in schizophrenia.

During the COVID-19 pandemic, a statistically significant increase in the incidence of Guillain-Barré syndrome (GBS) has begun to be observed. This article discusses the impact of immunological processes on structural and functional changes in the peripheral nervous system on the pathogenesis of GBS. The aim of the systematic review is to analyze and discuss available information from the scientific literature regarding a possible clinical relationship between SARS-CoV-2 infection along with vaccination mainly, adenovector and mRNA vaccines and the development of different types of Guillain-Barré syndrome. The review specifically discusses the role of proinflammatory cytokines and "cytokine storm" in patients with COVID-19 and their potential impact on the phenomenon of "molecular mimicry" and the generation of autoantibodies in GBS. This issue has been expanded to include information from studies on the impact of vaccination against SARS-CoV-2 virus and the higher number of observed cases of Guillain-Barré syndrome. Focusing on the characteristics of the methods, materials, results and conclusions, the review finally included 114 publications, like studies, meta-analyses, clinical cases and reviews. The systematic review was conducted using PubMed, Google Scholar, and Elsevier databases. It pointed out the molecular and clinical association between SARS-CoV-2 virus infections and COVID-19 vaccination, in the development of Guillain-Barré syndrome in the context of its clinical course.