Journal of NeuroVirology最新文献

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.

COVID-19 was a nightmare in humankind's history that challenged our advanced medical technology. All credit goes to the researchers who played a crucial role in curbing COVID-19 and proved our medical technology supremacy. However, COVID-19 has left some mysterious scars on human well-being. It is believed that COVID-19 has a significant negative impact on various cardiovascular (CVS) and central nervous system (CNS) diseases, especially in the case of CNS diseases like Alzheimer's. Surprisingly, COVID-19 affects the respiratory system, whereas Alzheimer's disease (AD) alters brain function. To explain this phenomenon, several hypotheses were proposed, but the mechanism needs to be clearly understood. Another critical thing to be concerned about is that COVID-19 will worsen pre-existing conditions and lead to the onset of AD. In the race to curb COVID-19, the invention of vaccines was speeded up, and it is necessary to fight against COVID-19. However, postvaccination follow-up is mandatory when an individual is a victim of AD. In this review article, we compiled the various dreadful effects of the COVID-19 virus on AD, the Post effects of the virus on AD, and the effect of the COVID-19 vaccination on AD. This article provides a new direction for research concerning COVID-19 and AD.

There is an urgent need to find an effective therapy for life-threatening HTLV-1-associated diseases. Bitter melon (Momordica charantia) is considered a traditional herb with antiviral and anticancer properties and was tested in this study on HTLV-1 infectivity. GC-MS analyzed the alcoholic extract. In vitro assay was carried out using transfection of HUVEC cells by HTLV-1-MT2 cell line. The cells were exposed to alcoholic and aqueous extracts at 5,10, and 20 µg/mL concentrations. In vivo, mice were divided into four groups. Three groups were treated with HTLV-1-MT-2 cells as test groups and positive control, and PBS as the negative control group in the presence and absence of M. charantia extracts. Peripheral blood mononuclear cells (PBMCs), mesenteric lymph nodes (MLNs), and splenocytes were collected for HTLV-1-proviral load (PVL) assessment, TaqMan-qPCR. The GC-MS analysis revealed 36 components in M. charantia. The studies showed significant reductions in HTLV-1-PVL in the presence of extract in the HUVEC-treated groups (P = 0.001). Furthermore, the inhibitory effects of extracts on HTLV-1 infected mice showed significant differences in HTLV-1-PVL among M. charantia treated groups with untreated (P = 0.001). The T-cells in MLNs were significantly more susceptible to HTLV-1 than others (P = 0.001). There were significant differences among HTLV-1-infected cells in MLNs and splenocytes (P = 0.001 and 0.046, respectively). Also, aqueous and alcoholic extract-treated groups significantly affected HTLV-1-infected PBMCs (P = 0.002 and 0.009, respectively). M. charantia may have effective antiviral properties. The substantial compound of M. charantia could have inhibitory effects on the proliferation and transmission of HTLV-1 oncovirus.