Journal of NeuroVirology最新文献

A 62-year-old man developed HSV-1 encephalitis with involvement of the left fronto-temporal lobes and caudate nucleus, improving under acyclovir. One month later, he developed mild word-finding difficulty. MRI showed the emergence of ring-enhancing nodular lesions with surrounding edema, confined to previously affected areas. Extensive repeat investigations revealed no alternative diagnosis. The patient recovered and remained clinically stable during follow-up. MRI over three years showed slow regression of the nodular lesions. A lumbar puncture at 3.5 years confirmed ongoing intrathecal immunoglobulin synthesis, with HSV-1-specific intrathecal synthesis. This case illustrates a rare post-herpetic granulomatous evolution, previously reported in only a few adults.

Neurodegenerative diseases such as Alzheimer's and Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS) pose a global health challenge due to their progressive course and lack of curative therapies. These conditions lead to severe neurological decline, significantly impacting patient independence and quality of life, and ultimately result in lethal outcome. Emerging evidence suggests that viral infections contribute to the onset and progression of these neurological diseases, Leblanc and Vorberg (PLoS Pathog 18:e1010670, 2022), either by directly inducing neurological symptoms or by triggering immune responses resulting in neuropathology. Nevertheless, systematic studies of the direct interplay between viral and host proteins in neurodegeneration remain scarce. A key aspect of viral pathogenesis is direct interaction between viral and host proteins (protein-protein interactions, PPIs), which are essential for viral replication and can disrupt or redirect host cell function Kim et al. (Nat Biotechnol, 2022); Zhou et al. (Res Sq, 2022), potentially contributing to the development of diseases traditionally considered non-communicable. Understanding these molecular mechanisms is crucial for advancing diagnostic and therapeutic strategies in neurodegenerative conditions, particularly ALS and MS. To enable systematic studies of these interactions, we introduce NeuroViOme as ORFeome resource encompassing nearly all protein-coding sequences from nine viruses selected based on their prevalence, neurotropism, and mechanistic or epidemiological links to neurodegenerative processes. NeuroViOme includes ORFs from Enteroviruses (EV-A71, EV-D68, CVB3, Echovirus E30), Herpesviruses (HSV-1, EBV, HHV3/Varicella Zoster), the endogenous retrovirus HERV-K, and Polyomavirus JCPyV. To our knowledge, this represents the most comprehensive viral ORF set assembled for neurodegeneration research to date. The collection builds the foundation for interactome mapping and functional genomics analyses and provides a valuable basis for systematic studies of viral perturbations of host pathways.

Human immunodeficiency virus (HIV) negatively impacts behavioral health and is co-morbid with neurocognitive and psychiatric disorders, most notably substance use disorder (SUD). Neuroimaging studies repeatedly show diminished functional connectivity in people living with HIV (PLWH). However, previous studies appear to disregard any potential for HIV/SUD co-morbidities, an oversight that represents a potential confound in HIV-related neuroimaging literature. Further, the functional connectivity of limbic neural substrates underlying reward and SUD (e.g., nucleus accumbens, amygdala, and hippocampus) remain unexplored in HIV. Here, we obtained resting-state functional magnetic resonance imaging (rsfMRI) data from a small population of HIV-positive people with no history of SUD. Functional connectivity in people with HIV was generally reduced relative to controls, with the greatest differences occurring between visual cortex and cerebellar vermis and nodules also associated with non-motor functions of cerebellum. Seed-based analyses of left and right nucleus accumbens (NAcc) and hippocampus (Hippo) yielded robust connections with the default mode network in controls. In PLWH, connectivity between NAcc or Hippo as seed recruited the default mode and inferior temporal networks to a lesser extent. Similar seed-based analyses of the amygdala in controls yielded robust connections with inferior temporal lobe regions rather than the default mode network, and exhibited anti-correlations with the executive network. Our results suggest that (1) people with HIV and no SUD history show reduced overall functional connectivity relative to controls, consistent with previous rsfMRI studies of people with HIV, and (2) this reduced connectivity in people with HIV extends to limbic structures underlying reward, even in the absence of SUD.

Human T-cell Lymphotropic virus type 1 (HTLV-1) is a retrovirus that infected 10-20 million of individuals worldwide. HTLV-1 infection is associated with the development of various diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). HAM/TSP is a chronic progressive neuroinflammatory disease characterized by motor impairment, spasticity, and other neurological manifestations. This narrative review provides a comprehensive overview of HAM/TSP following HTLV-1 infection. We discussed the virology and epidemiology of HTLV-1, transmission modes, and risk factors for infection. Furthermore, we delved into the pathogenesis of HAM/TSP disease, exploring the role of neuroimmunology and immune dysregulation. Viral proteins and host genetic factors that influence disease progression are also examined. Diagnostic approaches, including laboratory tests and imaging techniques, are discussed, along with available treatment options and immunomodulatory therapies. Additionally, we highlighted the history of HAM/TSP disease and provide insights into the global distribution and epidemiology. Finally, the current status and challenges of HTLV-1 vaccine development are addressed. This narrative review aims to enhance understanding of HAM/TSP disease following HTLV-1 infection, shedding light on key aspects of their etiology, diagnosis, and management, while emphasizing the need for continued research and public health interventions.

Background: HIV-associated neurocognitive impairment (HAND) is a common complication of HIV-1 infection, which can be exacerbated by exposure to cigarette smoke (CS). Tight junction proteins (TJPs) of the blood-brain barrier (BBB) play a crucial role in maintaining BBB integrity and preventing the entry of circulating toxic factors, including those resulting from HIV-1 infection, into the central nervous system. Both CS exposure and HIV-1 infection can independently disrupt TJPs and compromise BBB integrity; however, the combined or individual effects of these factors on BBB TJPs remain poorly understood.

Methods: An in vitro BBB comprised of Sprague-Dawley rat brain microvascular endothelial cell (RBMVEC) transwell cultures was exposed to wild-type (WT) and HIV-1 transgenic (TG) rat sera, alone or in combination with cigarette smoke extract (CSE) and analyzed for trans-endothelial electrical resistance (TEER) and paracellular permeability to 10 kDa fluorescein isothiocyanate (FITC)-dextran. Immunofluorescence staining was performed to assess the effects of treatment on the cellular localization and expression of the TJPs, "zonula occludens-1 (ZO-1) and claudin-5.

Results: Pretreatment TEER measures were significantly higher for cultures treated with WT serum alone compared to those treated with TG serum or with CSE. Compared to pretreatment, TEER measures were significantly reduced by treatment with WT serum alone, CSE alone, WT serum + CSE, and TG serum + CSE. TG serum alone or TG serum + CSE resulted in statistically significant increased permeability compared to WT serum. All treatments decreased TJP staining intensity, and, in some cases, altered TJP localization. These effects were most prominent following incubation with either CSE alone, TG serum alone, or TG serum + CSE.

Conclusions: CSE and TG serum induced separate and additive toxic effects on BBB function and integrity, which may underlie mechanisms that are associated with more severe HAND among HIV+ cigarette smokers.

Human herpesviruses (HHVs) cause central nervous system (CNS) infections; however, the role of neural autoantibodies remains unclear. We aimed to assess the presence of anti-N-methyl-D-aspartate receptor (anti-NMDAR) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in HHV-associated CNS infections. Seventeen adults with HHV DNA in the cerebrospinal fluid were tested using flow cytometry-based assays. None of the patients tested positive for anti-NMDAR antibodies. Anti-MOG antibodies were detected in two patients with VZV-associated CNS infection, one appearing after deterioration and the other at onset. Both patients recovered without sequelae. Anti-MOG antibodies may arise in VZV-associated CNS infections, warranting the consideration of autoimmune mechanisms.

Drugs inhibiting the cyclin-dependent kinases (CDK) 4 and 6 are widely used for the treatment of luminal breast cancer, in the adjuvant and in the metastatic setting, and adverse events are well-known. Progressive multifocal leukoencephalopathy (PML) is classically linked to immunosuppression. We present a case of progressive multifocal leukoencephalopathy that developed during adjuvant abemaciclib therapy in a seventy-year-old woman diagnosed with locally advanced ductal carcinoma of the breast. Neurological impairment developed after 18 months of initiating abemaciclib and in imaging tests a left frontal brain lesion appeared. Metastasis was excluded and the evidence of the John Cunningham polyomavirus (JCPyV) genome, both in the blood and in the cerebrospinal fluid, supported the diagnosis of PML. We did not identify significant immune blood cell counts alterations, nor other causes of immunosuppression; the patient was not treated with other immunosuppressive drugs. We speculate that different immune mechanism alterations related to abemaciclib, which has a high penetration rate in the brain, may be involved in an increased risk of JCPyV reactivation and consequently PML development.