Journal of NeuroVirology最新文献

During the COVID-19 pandemic, neuropsychiatric disorders began to be observed in a significant proportion of patients, occurring at different times after infection and characterised by varying degrees of severity. This article discusses neurological and psychiatric disorders associated with SARS-CoV-2 virus infection, taking into account biological pathomechanisms and psychosocial factors. The long COVID-19 along with the "brain fog" phenomenon were considered in the study. The purpose of the study is to analyse and discuss the available information from the scientific literature on the possible association between SARS-CoV-2 virus infection and the occurrence of neuropsychiatric disorders with different degrees of severity and temporal correlation. To discuss the correlation of COVID-19 with the occurrence of neuropsychiatric disorders, a systematic literature review was conducted using the following databases: PubMed, Elsevier and Google Scholar. The following keywords were used when searching the materials used: "neuropsychiatric disorders", "COVID-19", "SARS-CoV-2", "NeuroCOVID", "cytokine storm" and "long COVID-19". Focusing on the characteristics of the materials and methods used, as well as the results obtained and conclusions reached in each article, 164 publications of research, meta-analysis, review and case reports were included in the study. Neuropsychiatric disorders resulting from SARS-CoV-2 virus infection are multifactorial in nature. The main elements responsible for the varied pattern of symptoms include direct and indirect central nervous system effects of the disease, individual patient conditions, psychosocial factors, severity of immune responses and severity of infection. The neuropsychiatric effects of SARS-CoV-2 infection can be divided into symptoms directly related to the neurological and psychiatric zones and mixed disorders.

Background: Human herpesviruses (HHVs) are lifelong pathogens that can reactivate under stress or immunological changes. Depression has been implicated as both a potential trigger for and a consequence of HHV reactivation. This study investigates the bidirectional relationship between HHV reactivation and depression through a systematic review and meta-analysis.

Methods: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD42024565616). A search of PubMed, Web of Science, Embase, and Scopus identified studies published through March 5, 2024.

Results: Nineteen studies, representing a total sample size of 94,194 participants, were included in the meta-analysis. The pooled odds ratio (OR) demonstrated a significant association between HHV reactivation and depression (OR = 1.33; 95% CI: 1.07-1.64; p < 0.001; I² = 92%). Subgroup analyses revealed significant associations for Epstein-Barr virus (EBV) (OR = 1.99; 95% CI: 1.80-2.20) and herpes simplex virus 2 (HSV-2) (OR = 1.83; 95% CI: 1.32-2.55), while cytomegalovirus (CMV) and HSV-1 showed non-significant associations. A secondary meta-analysis found a significant association between pre-morbid depression and EBV reactivation (OR = 2.18; 95% CI: 1.48-3.21) as well as varicella-zoster virus (VZV) reactivation (HR = 1.09; 95% CI: 1.06-1.13). Sensitivity analyses confirmed the robustness of the findings, and no substantial publication bias was detected.

Conclusion: This study provides evidence of a bidirectional relationship between HHV reactivation and depression, highlighting depression as both a risk factor for and a potential consequence of HHV reactivation.

Progressive Multifocal Leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system (CNS) caused by human polyomavirus JC virus, with high mortality rate in people living with HIV (PLWH), without an effective specific treatment beside combined antiretroviral therapy (cART). The use of Pembrolizumab, an inhibitor of the Programmed cell death protein 1 (PD-1) receptor on T cells, has been associated with decreased viral clearance. Aim of this study is to evaluate clinical course of PLWH affected by PML treated with pembrolizumab. We report four consecutive PLWH with clinical and radiological evidence of PML and JCV-DNA detection in cerebrospinal fluid (CSF). Pembrolizumab was administered to all four PLWH alongside cART. Radiological and laboratory follow-up were performed at the end of the medical protocol. Clinically, 3 out of 4 PLWH showed an improvement in neurological deficits, partially reacquiring the lost functions, and they are alive at 3.5 years, 14 months, and 9 months, respectively; the fourth patient died shortly after treatment due to worsening respiratory conditions. In all the PLWH completing treatment, a decrease of about 80-90% of the specific PD-1 activity was observed. Prolonged survival and stabilization of radiological findings have been observed, along with clinical improvement and partial recovery of acquired deficits in 3 out of 4 PLWH. In addition, a decrease in anti-PD-1 expression has also been observed, suggesting a link between the therapy and the success achieved. Given the small sample and conflicting evidence in the existing literature, further investigation is needed to assess its effectiveness.

Oxidized low density lipoprotein receptor 1 (OLR1), a type II integral membrane glycoprotein, is involved in multiple neurological diseases. However, the roles and mechanisms of OLR1 in HIV-associated neurocognitive disorder (HAND) remain unclear. In the central nervous system, Transactivator of transcription (Tat) induces inflammatory response in microglia, thereby leading to neuronal apoptosis. In the present study, we demonstrated that OLR1 expression was upregulated during ectopic expression of Tat or soluble Tat stimulus in BV-2 microglial cells. Moreover, OLR1 signaling was proved to facilitate Tat-triggered inflammatory response and alleviated the microglia-derived conditioned media-mediated HT-22 neural cells apoptosis in a NF-κB-dependent manner. Conversely, Tat augmented OLR1 expression via NF-κB signaling pathway. Finally, in mouse models, we determined that silencing of OLR1 significantly ameliorated Tat‑induced neuroinflammation and hippocampal neuronal death. Taken together, our study clarifies the potential role of the OLR1/NF-κB feedback loop in Tat-induced microglial inflammatory response and neuronal apoptosis, which could be a novel therapeutic target for relief of HAND.

Few experts remain in the United States on the infectious vaccine-preventable neurological diseases (VPNDs). This is a mark of the changing epidemiology that has come with publicly available, often free, and sometimes mandated vaccinations in the U.S.A. over recent decades. Three main challenges to maintaining the battle against VPNDs exist in the U.S.A. today: (1) The variable uptake of vaccinations known to be safe and effective among the healthy U.S. population; (2) Waning awareness among physicians and community members on VPNDs; and (3) The global nature of travel, migration, medical tourism, and work. The mobility of the U.S. population and dependence on herd immunity in the USA for some residents may no longer be appropriate. This situation emphasizes the value of a global neurological disease framework for neurologists-in-training that could ultimately save lives in the USA. VPNDs must remain a part of the curriculum and board certification of both pediatric and adult neurologists in the USA given changes in U.S. policy and sentiment.

Bats are important reservoirs of zoonotic viruses, including the rabies virus (RABV), which causes rabies, a significant and fatal disease. In Brazil, RABV has been detected in several bat species. Interferon-induced protein with tetratricopeptide repeats 5 (IFIT5) is part of a group of interferon-stimulated genes (ISGs) known for their antiviral activity. This study investigated the interaction between batIFIT5 and different genetic lineages of RABV. The batIFIT5 was expressed in HEK-293T cells, which were infected with RABV genetic lineages isolated from Eptesicus furinalis (IP 964/06) and Tadarida brasiliensis (IP 3214/19), at varying infectious doses (pure, 100, 10, and 1). Direct immunofluorescence was performed to assess the effect of batIFIT5 on virus replication through the counting of fluorescent foci. Subsequently, after the expression of batIFIT5, 1 MOI was selected and used to evaluate the potential antiviral effect. Immunofluorescence was performed 24 and 48 h after infection. As a result, the viral concentration remained similar in the presence of batIFIT5 across distinct infectious doses. After infection with 1 MOI, a 30% reduction in infection rates was observed, particularly for the IP 3214/19 isolate after 24 h. These results highlight the potential antiviral role of IFIT5 against RABV infection.

The combination of antiretroviral therapy (cART) and preventive measures has significantly enhanced the management of Human Immunodeficiency Virus (HIV) infection. However, HIV-associated neurocognitive disorders (HAND) remain a challenge. This study aims to compare cognitive impairment (CI) assessments in people living with HIV/AIDS (PLWHA) using the International HIV Dementia Scale (IHDS), HIV Dementia Scale-Italian Version (HDS-IT) and MoCA (Montreal Cognitive Assessment), while also identifying significant associations. The cross-sectional study encompassed 294 outpatient PLWHA (median age: 57) on cART. Participants underwent cognitive, functional, and depression assessments, laboratory testing and CNS Penetration-Effectiveness (CPE) index assessment. IHDS, HDS-IT and MoCA identified CI in different proportions of PLWHA. Factors such as age, education level, infection duration, and substance use were associated with CI. The IHDS score (OR 0.79) and Level CD4 + T-lymphocytes nadir (OR 0.99) demonstrated independent and negative associations with the CPE-index. IHDS and MoCA tests appear to be useful for detecting CI in outpatient settings, enabling healthcare providers to conduct initial evaluations of PLWHA. IHDS assessment may be used for detecting CI related to high CPE regimens, while the MoCA provides a comprehensive assessment, also in domains not studied by IHDS. However, further research is needed to confirm these findings and refine their clinical applicability.

Microgravity (µg) during spaceflight affects cellular and molecular functions of both human cells and microbial pathogens, influencing viral replication and the host immune system. This study aimed to investigate the effects of simulated µg on Herpes Simplex Virus-1 (HSV-1) replication, host pro-inflammatory cytokine, and human endogenous retrovirus (HERV) activation in human neuroblastoma SH-SY5Y cells. Our results show that µg has a negative impact on HSV-1 replication, leading to significantly reduced viral titers and lower expression levels of HSV-1 early genes (ICP0, ICP4, and ICP27) compared to 1 gravity (1 g) conditions. Interestingly, despite lower viral titers and HSV-1 gene expressions under µg condition, we observed higher levels of HERVs and pro-inflammatory cytokine gene expression. In addition, there was a significant correlation between HSV-1 immediate-early genes with HERVs and pro-inflammatory cytokine gene expression, with stronger correlations observed under µg conditions. Taken together, µg reduces HSV-1 replication and increases host pro-inflammatory and HERVs gene expression, which demands further investigation for human health protection in space.

A 67-year-old woman with a history of follicular lymphoma and recurrent breast cancer with multiple metastasis developed PML during receiving fluvestrant plus palbociclib. Rituximab and bendamustine had finished 6.5 years ago. Discontinuing palbociclib and using mirtazapine, she is alive a year after diagnosis of PML. It is rare for PML to be diagnosed long after the last dose of rituximab and bendamustine. We will discuss the possible involvement of palbociclib in the course of PML.