Journal of NeuroVirology最新文献

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.

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.

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.

The effectiveness of COVID-19 vaccination is still unclear in individuals with underlying diseases such as HTLV-1 infection. This retrospective cohort study aimed to evaluate the humoral response of COVID-19 vaccines among people living with HTLV-1 (PLHTLV) in northeastern Iran. From December 2021 to October 2022, eighty-six HTLV-1⁺ subjects (50 males and 36 females; 47.7 ± 11.2 years) and 90 HTLV-1 seronegative individuals (age- and sex-matched convenient samples) were enrolled. The humoral immune response was evaluated by measuring different COVID-19 Abs in serum samples at least 28 days after receiving 2^nd or 3^rd doses of COVID-19 vaccines. Throughout all three rounds of immunization, Sinopharm was the most commonly used COVID-19 vaccine across all three immunization rounds. Compared to the HTLV-1^- group, a significantly lower frequency of all four Abs activity was observed among PLHTLV:anti-nucleocapsid (66.3% vs 86.7%, p = 0·001), anti-spike (91.9% vs 98.9%, p = 0·027), RBD (90.7% vs 97.8%, p = 0·043), and neutralizing Abs (75.6% vs 95.5%, p < 0·001). Also, the frequency of all Abs in 28 patients with HAM/TSP was higher than that of 58 asymptomatic carriers, although this difference was statistically significant only in the case of anti-spike Abs (p = 0.002). Notably, PLHTLV-vaccinated against COVID-19 demonstrated significantly lower antibody activities, indicating a reduced humoral immune response to COVID-19 vaccines.

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.

The role of plasma exosomes from people living with HIV (PLWH) with HAND in the phenotypic profile of uninfected monocytes remains unknown. We hypothesized that these exosomes influence the CD14/CD16 phenotypical profile of uninfected monocytes in a time-dependent manner. Exosomes were collected via ultracentrifugation from the plasma of women living with HIV (WLWH) and healthy controls stratified according to their cognition into normal cognition (NC) or symptomatic neurocognitive impairment (SNI) groups. Monocyte subsets were identified via flow cytometry by using anti-CD14 and anti-CD16 fluorescent antibodies. Exosome uptake and changes in the percentages of monocyte subpopulations were analyzed from 1 to 24 h. The following results were obtained. (1) The uptake of HIV-negative exosomes by total uninfected monocytes was observed at 24 h, whereas the uptake of HIV-positive exosomes was observed at an earlier time point at 6 h. (2) HIV-positive exosomes significantly decreased the percentage of classical monocytes and increased intermediate and nonclassical monocytes at 24 h. (3) The uptake of NC exosomes was observed at an early time point at 6 h compared with SNI in all of the monocyte subsets. (4) Higher percentages of monocyte subsets were observed when cells were exposed to NC exosomes at 1 h, 6 h, or 24 h than when monocytes were exposed to exosomes from SNI patients. Our findings may help to identify new targets and molecular mechanisms that are involved in the pathogenesis of HAND.

Human immunodeficiency virus (HIV) associated motor neuron disease (MND) is very rare. HIV infection can cause an MND-like syndrome due to central nervous system (CNS) involvement de novo or during antiretroviral therapy (ART) due to CNS escape. We present two cases: one with a classic amyotrophic lateral sclerosis (ALS) phenotype, which was the manifestation of symptomatic CNS escape from ART, and the second with a primary lateral sclerosis (PLS) phenotype associated with underlying HIV infection. A systematic review of published literature of people living with HIV (PLHIV) who developed ALS/ MND was conducted using the PubMed, Embase, and Lilacs databases. A total of 91 cases were found, 89 of which were obtained from 37 articles, and two were included from our own case series. In patients with HIV-associated MND, 63 patients reviewed had a classic ALS phenotype followed by progressive muscular atrophy variant (12), progressive bulbar palsy (8), PLS (7) and bulbar onset ALS (1). Neuroimaging, electrophysiology, cerebrospinal fluid (CSF) analysis, CSF and serum HIV viral load, and CD4 count investigations were used for diagnosis. Following the initiation or modification of antiretroviral therapy (ART), approximately 70% exhibited an improvement or a stable disease course. HIV-associated MND is a rare condition that can occur in both ART-naive individuals and those on treatment. A proportion of cases (~ 70%) show improvement with ART. Accurate diagnosis requires the exclusion of opportunistic infections, which remains a critical yet challenging aspect of managing this condition.

Choroid plexus (CP) inflammation can be quantified in vivo with MRI in people with multiple sclerosis (pwMS). It remains unknown whether Epstein Barr Virus (EBV) is related to CP changes. Total of 170 pwMS (116 relapsing-remitting; RRMS and 54 progressive MS; PMS) underwent MRI examination and measurement of humoral anti-EBV response. CP volume and CP pseudo-T2 (pT2), a relaxation time indicative of edema and neuroinflammation, were measured. Moreover, anti-EBV nuclear antigen-1 (EBNA-1) IgG and anti-EBV capsid antigen (VCA) IgG antibodies were measured. The PMS group had greater CP pT2 value when compared to RRMS (1120ms vs. 954ms, p = 0.037). After adjusting for age and therapy effects, higher CP pT2 values were associated with higher anti-EBNA-1 IgG levels only in PMS (r = 0.352, p = 0.015). Higher Anti-EBV humoral response in pwMS may be associated with increased CP neuroinflammatory changes and may be more relevant for the later chronic stage of the disease. Large-scale studies should investigate whether these findings are generalizable to all types of progressive MS.

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.

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.