Journal of NeuroVirology最新文献

Persistent intrathecal immune activation and neuronal injury remain common in people with HIV (PWH) despite effective antiretroviral therapy (ART). We examined longitudinal trajectories of cerebrospinal fluid (CSF) neurofilament light (NfL), a marker of axonal injury, together with neuroinflammatory biomarkers following ART initiation. Ninety-nine PWH from the Gothenburg HIV CSF Study Cohort who achieved viral suppression were included, with CSF samples collected before and after treatment initiation. NfL and a panel of biomarkers including YKL-40, sTREM-2, neopterin, and GFAP were analyzed. CSF NfL declined rapidly, from a mean of 673 ng/L at baseline to 592 ng/L after three months and 490 ng/L after twelve months. All inflammatory biomarkers showed parallel and significant decreases. Prior to ART, 25% of participants had elevated NfL levels; this subgroup displayed higher baseline inflammation, and the steepest biomarker declines after treatment initiation. In participants with normal baseline NfL, inflammatory markers decreased while NfL remained stable. Beyond one year, no further reductions were evident. These longitudinal findings demonstrate that ART rapidly and effectively reduces CSF biomarkers of neuronal injury and neuroinflammation in HIV, with the greatest benefit in individuals with baseline axonal damage.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder of the central nervous system (CNS) caused by reactivation of the John Cunningham (JC) polyomavirus, commonly occurring in immunosuppressed individuals. Comparative data on the clinical and neuroimaging features of PML in human immunodeficiency virus (HIV)-positive and HIV-negative patients from India remain scarce. To compare clinical profiles, neuroimaging characteristics, and outcomes of HIV-positive and HIV-negative PML patients with cerebrospinal fluid (CSF) JC virus polymerase chain reaction (PCR) or brain biopsy PCR confirmation. This single-centre ambispective cohort study included adults (age ≥ 18 years) presenting to a tertiary care hospital in India between January 2019 - July 2025, who were diagnosed with PML. Demographic, clinical, laboratory, imaging and outcome data were collected. These were thereafter compared between the HIV-positive and HIV-negative PML cohorts. We recruited 41 PML patients out of 100 who were screened during the study period. Of these, 29 (70.7%) were HIV-positive and 12 (29.3%) were HIV-negative. HIV positive PML patients were younger [Mean age: (42 ± 10.5 vs 50 ± 13.4 years, p-value = 0.05)] and presented with a shorter symptom duration [4.2 ± 2.2 months vs 7.1 ± 5.3 months (p-value = 0.02)] compared to the HIV-negative cohort. Cognitive impairment (53.6% overall) was the most common symptom overall, with altered sensorium [27.6% vs 16.7% (p = 0.694)] and cerebellar ataxia [41.4% vs 25% (p = 0.480)] observed more commonly in HIV-positive patients and hemiparesis [66.7% vs 44.8% (p = 0.306)] manifesting more frequently in HIV-negative cases. However, these were not statistically significant. Radiologically, multifocal lesions (56.1%) were most commonly seen. Infratentorial involvement [72.3% vs 50% (p-value = 0.491)] and multifocal/diffuse lesions [86.2% vs 75% (p-value = 0.491)] were more common in HIV-positive, although these did not attain statistical significance. The shrimp sign was more common in patients with HIV [37.9% vs 25% (p = 0.003)]. Twenty-six patients (63.4%) showed symptomatic improvement with treatment, while six (14.6%) worsened and nine (22%) succumbed to their illness. Adult HIV-positive PML patients present earlier and tend to have diffuse, infratentorial and deep grey matter involvement. Adult HIV-negative PML patients frequently exhibit focal or punctate lesions. Certain imaging features, such as the shrimp sign in HIV-positive patients and the milky way sign in HIV-negative patients, may provide valuable diagnostic clues, but are not definitive and require confirmation in larger studies. PML patients may show clinical improvement if early therapy for the etiology of PML is provided.

This study aimed to investigate the clinical features of varicella-zoster virus (VZV) meningitis cases diagnosed by polymerase chain reaction (PCR) despite normal routine cerebrospinal fluid (CSF) testing. A retrospective review was performed on hospitalized central nervous system (CNS) infection cases at our institution from 2013 to 2024. VZV meningitis cases were analyzed and divided into two groups: those diagnosed by positive PCR without routine CSF abnormalities (PCR Group) and those with routine CSF abnormalities (Usual Group). PCR methods included conventional techniques and a rapid detection system (FilmArray^®). Among 75 CNS infection cases (49 viral, 13 bacterial, 6 tuberculosis, 2 fungal, and 1 amoebic), 29 VZV meningitis cases were identified. Compared to the Usual Group (n = 25), the PCR Group (n = 4) had significantly lower CSF cell counts (median 1.0 vs. 99.0/µl, p < 0.001) and protein levels (44.0 vs. 70.0 mg/dl, p < 0.001) but similar glucose levels (58.0 vs. 54.0 mg/dl, p = 0.17). All PCR Group cases were female (vs. 52% in the Usual Group), had a trigeminal skin rash (vs. 52%), and presented with headache without meningeal irritation signs (vs. 44.0%) or fever. 50% of cases in the PCR Group were immunocompromised (vs.24%). Other clinical and epidemiological features were similar in both groups. Routine CSF analysis may fail to reveal abnormalities in VZV meningitis, particularly in both immunocompromised and immunocompetent female patients presenting with trigeminal skin rash and headache in the absence of meningeal irritation signs or fever. PCR is recommended to facilitate prompt and accurate diagnosis in such cases.

COVID-19 is a systemic infection that causes endothelial dysfunction, contributing to severe cases. While vascular complications are well-documented, their impact on vascular structure, function, and cognition remains unclear. This cross-sectional study explored vascular and cognitive differences across patients with mild, moderate, and severe COVID-19, examining correlations between global cognitive performance and vascular parameters. This study included 83 working-age patients (30-65 years, both sexes) who recovered from COVID-19 within 6-12 months. They were grouped by severity: mild (outpatients, no oxygen support), moderate (hospitalized, conventional oxygen therapy), and severe (hospitalized, advanced oxygen therapy). Exclusions included pre-existing cognitive or neurological conditions, significant atherosclerosis, malignancies, and prior COVID-19 vaccination. Global cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) test, while vascular parameters - carotid intima-media thickness (IMT), beta stiffness index (β index), mean flow velocity (MVs), maximum velocity after breath-holding (MV-BH), and breath-holding index (BHI) - were evaluated using duplex ultrasound and transcranial Doppler. Patients with severe COVID-19 had the highest carotid stiffness and poorest cerebrovascular reactivity. While MoCA scores showed no significant group differences, 23-40% had mild cognitive impairment. MoCA scores negatively correlated with β index in mild group (ρ=--0.453; p = 0.034), while MVs positively correlated with MoCA in severe cases (ρ = 0.414; p = 0.028). The association between arterial stiffness and cognitive impairment in mild cases, suggests lasting effects of SARS-CoV-2 rather than pre-existing conditions. These findings highlight carotid stiffness as a key factor in post-COVID-19 cognitive impairment, emphasizing early risk identification for timely intervention.

Angiotensin-converting enzyme 2 (ACE2), a key regulator of the renin-angiotensin system (RAS), maintains central nervous system (CNS) homeostasis by metabolizing neuroinflammatory peptides like angiotensin II (Ang II) and apelin-13, thereby exerting neuroprotective effects. Recent evidence underscores ACE2's paradoxical roles in neurodegeneration: its loss of function due to SARS-CoV-2 spike protein binding exacerbates neuroinflammation and cognitive decline, while its upregulation may mitigate AD pathology by reducing amyloid-β (Aβ) accumulation and tau hyperphosphorylation. The COVID-19 pandemic has further highlighted ACE2 axis dysregulation as a potential accelerator of AD progression, with studies reporting elevated biomarkers of neurodegeneration in post-COVID patients. Therefore, in this review, we highlight the emerging insights into ACE2's dual role in AD and other neurodegenerative diseases, emphasizing its interactions with microglial activation, blood-brain barrier integrity, and mitochondrial dysfunction. We also critically evaluate novel therapeutic strategies, including recombinant ACE2, ACE2-derived peptides, and gene therapy approaches designed to restore RAS balance without compromising viral defense mechanisms. By integrating mechanistic and clinical insights, this work highlights ACE2 as a promising target for neurodegenerative disease interventions.

Alphaherpesviruses such as Herpes Simplex Virus 1 (HSV-1) and Pseudorabies virus (PrV) invade the central nervous system (CNS) via peripheral nerves. While olfactory and trigeminal pathways are well-known, additional cranial routes remain underexplored. Using a PrV-∆UL21gfp/US3∆kin mutant in CD1 mice, we mapped early neuroinvasion (4-96 hpi) by immunofluorescence and RNA in situ hybridization. Viral antigen and lytic viral gene expression (UL19 RNA) were detected in the olfactory epithelium, vomeronasal organ, incisors, palate, olfactory bulb, and brainstem. These results indicate multineural CNS access involving olfactory (I), trigeminal (V), glossopharyngeal (IX), and hypoglossal (XII) nerves, highlighting this model's value for studying early alphaherpesvirus spread.

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.