Journal of NeuroVirology最新文献

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.

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.

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.

Metformin, a first-line drug used to treat type 2 diabetes mellitus (T2DM), also reduces neuroinflammation and improves motor and cognitive outcomes. Metformin binds to presenilin enhancer 2 (PEN2) and further enhances its therapeutic benefits. The mechanisms of HIV-associated neurocognitive disorders (HANDs) remain unclear. HIV-1 trans-activator of transcription (Tat) contributes to neurotoxicity in HAND. We revealed that PEN2 expression decreased markedly in HAND patients and Tat-infected microglia. Metformin (200 µM) treatment significantly reduced Tat-induced decreases in cell viability, oxidative stress, the proinflammatory response and excessive glutamate and iNOS release and had neuroprotective effects. Tat subsequently increased NF-κB activity, which was prominently suppressed during treatment. In addition, PEN2 knockdown in microglia dramatically reversed the neuroprotective effect of metformin against Tat. Our findings indicate that metformin binds PEN2 and modulates microglia-mediated HIV-1 Tat neurotoxicity in HAND.

Background: Postherpetic neuralgia (PHN) represents the most prevalent and distressing complication of shingles. The aim of this study was to explore the diagnostic significance of miR-34c-5p in PHN patients and to assess its correlation with rehabilitation effect.

Methods: This study enrolled 154 PHN patients and 108 healthy participants as research subjects. RT-qPCR was used to detect serum miR-34c-5p levels in the participants. ROC curve was employed to estimate the diagnostic significance of miR-34c-5p in PHN patients. Logistic regression analysis was performed to analyze the risk factors related to the occurrence of PHN. VAS, TEX-Q and HADS scales were filled in by questionnaires to analyze the rehabilitation effect of PHN patients after treatment. Spearman correlation analysis was applied to evaluate the relationship of miR-34c-5p levels with rehabilitation effect in treated PHN patients.

Results: miR-34c-5p levels were notably elevated in PHN patients compared to healthy participants. miR-34c-5 had a high sensitivity (79.2%) and specificity (84.3%) to distinguish between healthy individuals and PHN patients. Logistic regression analysis indicated that miR-34c-5p emerged as an independent risk factor for the development of PHN. miR-34c-5p levels, VAS, TEX-Q, HADS-A and HADS-D scores were reduced in prednisone-treated PHN patients compared to the basic treatment group. In addition, Spearman correlation suggested that miR-34c-5p levels were positively correlated with VAS, TEX-Q, HADS-A and HADS-D scores.

Conclusion: miR-34c-5p exhibited the ability to diagnose PHN and may be a biomarker for diagnosis of this disease. Moreover, reduced miR-34c-5p expression in PHN patients correlate with enhanced outcomes in rehabilitation.

Misuse of opioids is a major comorbidity in people with HIV (PWH). Neurological abnormalities and opioid addiction seen in PWH involve the interplay among signaling pathways. However, the impact of HIV proteins on morphine dependence is understudied. We aimed to understand the modulation of the opioid dependence genes and signaling pathways in the striatum (Str) and prefrontal cortex (PFC) of PWH. HIV-1 transgenic (HIV-1Tg) rats and F344 control animals were given 2 and 4 pellets of morphine (75-mg/pellet)/placebo on Days 1 and 2, respectively, via subcutaneous implantation. On Day 5, at morphine tolerance the rats were sacrificed, Str and PFC were collected for RNA isolation and cDNA preparation. A PCR-array was used to examine the expression of the 65 opioid dependance genes. Varying numbers of genes were significantly upregulated in the Str and PFC of morphine treated rats. Fold change values were uploaded to QIAGEN Ingenuity Pathway Analysis, to study the signaling pathways associated with the treatment conditions. CREB signaling in neurons and Neuroinflammation signaling pathway were highly activated in the Str of both male and female HIV-1Tg rats given morphine. Gαq signaling and S100 family signaling were activated in female HIV-1Tg rats received morphine. Similarly, in the PFC, synthesis of IP3, CREB Signaling in neurons, Gαq signaling in males and CREB Signaling in neuron, and Gαq signaling in females were activated. Using bioinformatic analysis, we identified key signaling pathways and gender dependent changes in the opioid dependent gene expression and pathway enrichment of HIV-1Tg rats at morphine tolerance.

The development of a comprehensive classification for herpesvirus encephalitis remains an urgent task. Distinct clinic-radiological forms of herpesvirus cerebral lesions have been characterized, including findings from histopathological studies. Differences among these forms have been demonstrated concerning key clinical and paraclinical parameters. The presented classification identifies several distinct forms of herpesvirus encephalitis: temporal, brainstem, limbic, diencephalic encephalitis, rhombencephalitis, leukoencephalitis, ventriculoencephalitis, diffuse glial micronodular encephalitis, subcortical and cortical encephalitis, cerebellitis, neonatal encephalitis. Additionally, the concepts of combined, coexisting and multimodal lesions are introduced to describe complex forms of herpesvirus neuroinfections. The use of the term "specific spectrum of herpesvirus cerebral lesions" is supported. Both the phenomena of specificity and universality are considered. Fundamental differences between the forms of herpesvirus encephalitis are highlighted with respect to their prevalence within the population, etiological factors, clinical manifestations, typical complications, recovery completeness, mortality rates, immune status. The distinctive diagnostic and therapeutic approaches required for each form of herpesvirus encephalitis are emphasized. The integration of this classification into clinical practice has the potential to optimize medical care for patients with herpesvirus encephalitis, enabling not only etiologically-oriented but also form-specific approaches to treatment.

HIV-associated neurocognitive disorders (HAND) pose significant challenges, particularly in individuals with comorbid opioid use disorder (OUD). Fentanyl, a potent synthetic opioid, is a leading contributor to opioid-related fatalities, yet its effects in the context of HIV remain poorly understood. This study investigated the differential impacts of fentanyl and morphine on neuroinflammatory signaling, blood-brain barrier (BBB) integrity, and antiretroviral (ARV) brain accumulation in EcoHIV-infected mice. C57BL/6 mice were assigned to morphine, fentanyl, or saline treatment groups, with or without EcoHIV infection. Tight junction proteins claudin-5 and ZO-1 were measured in striatum and hippocampus via ELISA, while proinflammatory chemokines were analyzed by multiplex assay. In EcoHIV-infected mice, both opioids significantly increased CCL2, CCL4, CCL5, and CCL11 concentrations in the striatum, with fentanyl causing greater increases in CCL2 than morphine. Additionally, fentanyl, but not morphine, significantly decreased CCL3 concentrations in the striatum. Principal component analysis revealed distinct treatment-specific patterns within the striatum, underscoring opioid-specific differences. Tight junction protein expression data demonstrate opioid-specific, sex-specific, and region-specific effects on the key BBB proteins, ZO-1 and claudin-5. Both opioids also reduced ARV brain concentrations in infected mice, with region- and opioid-specific effects. Fentanyl decreased dolutegravir in the hippocampus, while morphine decreased abacavir in both regions. These findings demonstrate that fentanyl and morphine exposure in the context of HIV produce distinct impacts on neuroinflammatory response, BBB integrity, and ARV brain exposure. Understanding these opioid-specific effects is critical for improving clinical outcomes and treatment strategies for individuals with HIV and OUD.