Journal of NeuroVirology最新文献

HIV-associated neurocognitive disorder (HAND) is a complication of chronic inflammation caused by HIV infection that impairs cognitive and motor functions. HAND can occur at any age, regardless of the duration of infection, even in people living with HIV (PLWH) whose blood viral load is controlled by antiretroviral therapy. The diagnosis of HAND requires a battery of neuropsychological tests, which is time-consuming and burdensome, limiting its effectiveness for screening PLWH. Here, we aimed to identify biomarkers for quantitatively diagnosing and screening for HAND using minimally invasive blood tests. Neuronal-derived exosomes (neuroexosomes) were isolated from the peripheral blood of PLWH, and the transcriptomes of their microRNAs (miRNAs) were analyzed. We identified five upregulated miRNAs (hsa-miR-16-5p, hsa-miR-26a-3p, hsa-92a-3p, hsa-miR-103a-3p, and hsa-miR-185-5p), and two downregulated miRNA (hsa-miR-3613-3p and hsa-miR-4668-5p) in PLWH diagnosed with HAND (HAND PLWH). Functional analysis of five miRNAs whose expression levels increased in HAND PLWH using the database showed that these miRNAs are involved in motor proteins and endocytosis, which are associated with nerve function. The expression levels of hsa-miR-16-5p, hsa-miR-103a-3p, and hsa-miR-185-5p were significantly higher than those in the non-HIV controls and non-HAND PLWH, suggesting that these miRNAs are potential biomarkers for HAND. Since there were no changes in known dementia miRNA biomarkers in HAND PLWH, the miRNAs identified in this study will allow for early differentiation of HAND.

Effective neuropsychological assessment of people with HIV (PWH) in low- and middle-income countries (LMICs) is hampered by the unavailability of adequate test norms. We aimed to: (1) develop demographically-corrected (regression-based) South African (SA) normative data for an HIV appropriate neuropsychological test battery for Xhosa home-language speakers; (2) compare the utility of those norms to that of (i) internal standardization norms and (ii) US test publisher norms; and (3) determine the criterion validity of the newly-developed norms. 114 controls and 102 demographically comparable Xhosa home-language people living with HIV completed a well-establised, standard HIV neuropsychological test battery assessing seven cognitive domains. Using a common performance metric (z-score), we compared control and PWH test performance and examined the extent to which the three different normative datasets embedded demographic effects e.g., education. Using internal standardization norms, analyses detected medium-sized correlations of overall test performance with age and education. Correlations were fully corrected for by the newly-developed demographically-corrected norms. Using demographically-corrected norms, PWH performed significantly more poorly than controls in five cognitive domains, whereas using internal standardization norms and test-publisher norms, PWH performed significantly more poorly than controls in one and two domains, respectively. Demographically-corrected norms estimated 43.1% of PWH were cognitively impaired; these estimates were 22.5% using test-publisher norms and 19.6% using internal standardization norms. Demographically-corrected SA norms were more sensitive to cognitive impairment in PWH than the other sets of norms. Expansion of this regression-based method to create population-appropriate norms will benefit research and clinical practice in LMICs.

Although antiretroviral therapy (ART) has dramatically improved the outlook of the HIV/AIDS pandemic, people living with HIV (PLWH) on suppressive therapy are still at higher risk for a range of comorbidities including cardiovascular disease (CVD) and HIV-associated neurocognitive disorders (HAND), among others. Chronic inflammation and immune activation are thought to be an underlying cause of these comorbidities. Many of the factors thought to drive chronic inflammation and immune activation in HIV overlap with factors known to induce trained immunity. Trained immunity is a form of innate immune memory that metabolically and epigenetically reprograms innate immune cells to mount enhanced inflammatory responses upon secondary encounter with unrelated inflammatory stimuli. While this phenotype has been characterized in a variety of disease states in animals and humans, very little is known about its potential contribution to chronic HIV pathogenesis. In this review, a broad overview of innate immune memory in the periphery and the central nervous system (CNS) is provided and the evidence for trained immunity in the context of HIV is considered. In PLWH on ART, this phenotype could contribute to the chronic inflammation and immune activation associated with HIV comorbidities and could complicate HIV cure strategies due to the potential persistence of the phenotype after eradication of the virus. Further research into this immune state in the context of HIV may open the door for new therapeutics aimed at treating HIV comorbidities like HAND.

Zika virus (ZIKV) is a neurotropic flavivirus that induces congenital Zika syndrome and neurodevelopmental disorders. Given that ZIKV can infect and replicate in neural cells, neurological complications in adult brain are also observed. Glial cells may emerge to delay and/or prevent the development of ZIKV-induced neurodegeneration. These cells actively participate in metabolic, inflammatory and redox processes, and consequently, in the pathophysiology of neurodegenerative diseases, including diabetic encephalopathy. In this sense, changes in glucose metabolism can support the inflammatory activity of astroglial cells; however, the effects of increased glucose concentration during ZIKV infection have not yet been explored in astroglial cells. Here, we evaluated functional parameters of astroglial cells exposed to ZIKV upon normal and high glucose concentrations, focusing on inflammatory profile, oxidative stress, and expression of critical genes for astroglial functions. High glucose potentiated the pro-inflammatory and oxidative effects of ZIKV, as well as potentiated the downregulation of signaling pathways, such as Nrf-2 (nuclear factor erythroid derived 2 like 2), sirtuin 1 (SIRT1), peroxisome proliferator activated receptor gamma coactivator 1-alpha (PGC-1α), and poly (ADP-ribose) polymerase (PARP). In summary, our results suggest that high glucose can favor the activation of inflammatory signaling while impairing cytoprotective pathways in astroglial cells exposed to ZIKV and reinforce the hypothesis that this virus is highly neurotrophic, with significant impact in glial cells.

Guillain-Barre Syndrome (GBS) is a rare but serious neurological disorder characterized by acute flaccid paralysis and areflexia, usually after an infectious disease. This case report describes a previously healthy 9-year-old boy who developed GBS following an acute hepatitis A infection. The patient presented with rapidly progressive weakness, ascending paralysis, and areflexia, confirmed by clinical and electrophysiological findings. Results were consistent with the GBS subgroup of Acute Motor Axonal Neuropathy. Treatment with intravenous immunoglobulin (IVIG) led to gradual improvement, highlighting the importance of early recognition and intervention. This report reviews the current literature on the association between GBS and hepatitis A, emphasizing the rarity of such cases in pediatric populations. The report aims to raise awareness among clinicians about this potential complication of hepatitis A, underscoring the need for prompt diagnosis and treatment to improve outcomes in similar cases. The report emphasizes the need for prompt diagnosis and treatment to improve outcomes in similar cases.

Antiretroviral treatment (ART) effectively suppresses viral loads in both plasma and cerebrospinal fluid (CSF). Patients with discordant plasma and CSF viral loads may experience chronic-progressive or fluctuating neurocognitive dysfunctions. This study examined the incidence of symptomatic CSF viral escape (CSFVE) in patients receiving ART. This retrospective cohort study was conducted between 2000 and 2023. The primary outcome measure was the incidence of symptomatic CSFVE. Nonparametric Mann-Whitney U and Fisher exact/χ 2 tests were applied for continuous and categorical variables, respectively. The cumulative incidence function with Gray's test was used to compare the incidence of CSFVE across the treatment regimens. During the study period, 52 of the 8415 patients were diagnosed with CSFVE. The median duration of HIV diagnosis in patients with CSF VE was 150 (12-288) months, with a median nadir CD4 + T-cell count 96.5 (13-601 cells/L)], and 75% of the patients were on a ritonavir-boosted protease inhibitor (PI/r) regimen. The cumulative incidence of symptomatic CSFVE at a follow-up of 14 years was 1% (95% CI, 0-1%). PI/r (HR 34.73; 95% CI 13.5 to 89.4; p < 0.001) and integrase strand transfer inhibitor (INSTI) (HR 3.42; 95% CI 1.94 to 6.02; p < 0.001) regimens were significantly more likely to be associated with CSFVE than the Non-nucleoside reverse transcriptase inhibitors (NNRTIs) regimens. NNRTIs had the lowest risk of CSFVE compared to the PI/r and INSTI regimens. A rapid and complete recovery is possible with symptomatic CSFVE if it is diagnosed and treated early.

Tick-borne encephalitis (TBE) is a vector-borne disease caused by the TBE virus (TBEV). Although TBEV infection in children seems to lead to a milder clinical presentation, data in pediatrics are scarce. We aimed to determine the incidence of TBE among pediatric patients presenting with neurological symptoms from January 2020 to December 2022 at the University Hospital of Strasbourg (HUS), France. 462 Patients for whom cerebrospinal fluid (CSF) samples were available were included and categorized by age group: 0-4 years, 5-9 years, and 10-15 years. Serological tests and RT-PCR were carried out on the CSF samples, and the positive results were confirmed by seroneutralization test (SNT). A CSF IL-6 assay was performed for confirmed cases. We retrospectively detected four TBE-confirmed cases. We found an incidence of 1.51 cases per 100,000 inhabitants in the pediatric population over 2020-2022. The four cases were girls, with a median age of 10.4 years. The symptoms appeared in two cases in October 2022, outside the seasonal peak. Signs of encephalitis were present in two patients, and persistent sequelae were reported in three patients and two more than a year after hospitalization. None of the confirmed cases were vaccinated against TBEV despite frequent exposure to ticks. Intrathecal concentrations of IL-6 were increased for two patients; for one patient, the concentration was significantly higher than the values found in control cases. Our data highlight the need for early diagnosis and long-term follow-up of affected children and raise questions about the evolution of vaccination recommendations.

Long COVID, also called post-acute sequelae of SARS-CoV-2 infection (PASC) affects millions of people in the world. The neurologic manifestations of PASC (Neuro-PASC) are among the most debilitating but they are largely unreported in Africa. We sought to compare the demographics, symptoms and cognitive profile of post-hospitalization Neuro-PASC (PNP) and non-hospitalized Neuro-PASC (NNP) patients in Nigeria. In this cross-sectional study performed at the Lagos University Teaching Hospital, 106/2319 (4.6%) SARS-CoV-2 positive individuals contacted via telephone reported Neuro-PASC symptoms with a higher frequency in PNP than in NNP individuals ((23/200 (11.5%) vs. 83/2119 (3.9%), p = < 0.0001). The predominant neurologic symptoms at any time during the disease course were difficulty remembering / brain fog (63/106; 59.4%), fatigue (59/106; 55.7%), sleep problems (34/106; 32%), headache (33/106; 31%), paresthesia (12/106; 11.3%), and myalgia (10/106; 9.4%). Of 66 participants with Neuro-PASC who underwent in-person neurological evaluation and cognitive screening, all had normal scores on the Intervention for Dementia in Elderly Africans cognition screen, while 11/65 (16.9%) that completed the Montreal Cognitive Assessment had results consistent with mild cognitive impairment (3/16 PNP (18.8%) and 8/49 NNP (16.3%); p = 1.0). Finally, 47/66 (71.2%) had digit span test scores consistent with mild cognitive dysfunction (12/16 PNP (75%) and 35/50 (70%) NNP; p = 1.0). Our findings reveal the previously unrecognized occurrence of Neuro-PASC among COVID-19 survivors in Nigeria and highlight the need for improved screening and diagnosis of Neuro-PASC in our population. Development of cognitive support services for persons suffering from Neuro-PASC in Nigeria is warranted.

We report two patients who developed atypical, disseminated herpes zoster infections while on dimethyl fumarate (DMF) treatment, one with varicella zoster virus (VZV) encephalitis and another with herpes zoster oticus resulting in lasting motor and sensory deficits. We recommend vaccination against VZV prior to DMF initiation be incorporated as standard of care, as ensuring patients are protected against VZV before starting DMF can prevent such severe outcomes.

Human endogenous retroviruses (HERVs) involvement in neurological diseases has been extensively documented, although the etiology of HERV reactivation remains unclear. MicroRNAs represent one of the potential regulatory mechanisms of HERV reactivation. We identified fourteen microRNAs predicted to bind the HERV-K transcript, and subsequently analyzed for their gene expression levels alongside those of HERV-K. We documented an increased expression of four microRNAs in patients with Parkinson's disease compared to healthy controls, which correlated with a downregulation of HERV-K transcripts. We hypothesize that specific microRNAs may bind to HERV-K transcripts, leading to its downregulation.