Journal of NeuroVirology最新文献

Encephalitis is a central nervous system disorder, often caused by infectious agents or aberrant immune responses. We investigated causes, comorbidities, costs, and outcomes of encephalitis in a population-based cohort. ICD-10 codes corresponding to encephalitis were used to identify health services records for all adults from 2004 to 2019. Data were cross-validated for identified diagnoses based on laboratory confirmation using univariate and multivariate statistical analyses. We identified persons with a diagnosis of encephalitis and abnormal cerebrospinal fluid (CSF) results (n = 581) in whom viral genome was detected (n = 315) in a population of 3.2 million adults from 2004 to 2019. Viral genome-positive CSF samples included HSV-1 (n = 133), VZV (n = 116), HSV-2 (n = 34), enterovirus (n = 4), EBV (n = 5), and CMV (n = 3) with the remaining viruses included JCV (n = 12) and HHV-6 (n = 1). The mean Charlson Comorbidity Index (2.0) and mortality rate (37.6%) were significantly higher in the CSF viral genome-negative encephalitis group although the mean costs of care were significantly higher for the CSF viral genome-positive group. Cumulative incidence rates showed increased CSF VZV detection in persons with encephalitis, which predominated in persons over 65 years with a higher mean Charlson index. We detected HSV-2 and VZV more frequently in CSF from encephalitis cases with greater material-social deprivation. The mean costs of care were significantly greater for HSV-1 encephalitis group. Encephalitis remains an important cause of neurological disability and death with a viral etiology in 54.2% of affected adults accompanied by substantial costs of care and mortality. Virus-associated encephalitis is evolving with increased VZV detection, especially in older persons.

Human immunodeficiency virus-1 (HIV-1) clade C is the most prevalent form of HIV-1 comprising nearly 46% of global infections and is the dominant subtype in India. Despite its predominance, the impact of HIV-1 clade C infection on cognitive function has been understudied in comparison with other subtypes, notably clade B, which is primarily found in Europe and North America. Few studies have assessed cognitive impairment in antiretroviral therapy (ART) naïve men and women with HIV-1 clade C infection. In this study conducted in Northern India, differences in neuropsychological functioning were compared between 109 participants (70 men, 39 women) with untreated HIV-1 clade C infection and 110 demographically matched healthy controls (74 men, 36 women). A comprehensive neuropsychological battery was used to examine depression, self-assessment of functioning, and cognitive performance in six domains of functioning. Group differences were assessed by HIV-1 status and sex, controlling for age and education. Results indicated that cognitive deficits were substantially greater among male participants with HIV-1 clade C compared to male controls in all domains of cognitive functioning; in contrast, women with HIV-1 clade C had only minor deficits compared to healthy female participants. In addition, a larger proportion of men with HIV-1 clade C exhibited high levels of depression than women with HIV-1 clade C. These findings suggest that untreated HIV-1 clade C infection in men can have debilitating effects on neuropsychological function and depression, and stress the importance of facilitating rapid access to treatment to reduce the impact of HIV-1 infection.

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.

Norovirus, a positive-stranded RNA virus, is one of the leading causes of acute gastroenteritis among all age groups worldwide. The neurological manifestations of norovirus are underrecognized, but several wide-spectrum neurological manifestations have been reported among infected individuals in the last few years. Our objective was to summarize the features of norovirus-associated neurological disorders based on the available literature. We used the existing PRISMA consensus statement. Data were collected from PubMed, EMBASE, Web of Science, and Scopus databases up to Jan 30, 2023, using pre-specified searching strategies. Twenty-one articles were selected for the qualitative synthesis. Among these, seven hundred and seventy-four patients with norovirus-associated neurological manifestations were reported. Most cases were seizure episodes, infection-induced encephalopathy, and immune-driven disorders. However, only a few studies have addressed the pathogenesis of norovirus-related neurological complications. The pathogenesis of these manifestations may be mediated by either neurotropism or aberrant immune-mediated injury, or both, depending on the affected system. Our review could help clinicians to recognize these neurological manifestations better and earlier while deepening the understanding of the pathogenesis of this viral infection.

Human immunodeficiency virus (HIV) and drug abuse are intertwined epidemics, leading to compromised adherence to combined antiretroviral therapy (cART) and exacerbation of NeuroHIV. As opioid abuse causes increased viral replication and load, leading to a further compromised immune system in people living with HIV (PLWH), it is paramount to address this comorbidity to reduce the NeuroHIV pathogenesis. Non-human primates are well-suited models to study mechanisms involved in HIV neuropathogenesis and provide a better understanding of the underlying mechanisms involved in the comorbidity of HIV and drug abuse, leading to the development of more effective treatments for PLWH. Additionally, using broader behavioral tests in these models can mimic mild NeuroHIV and aid in studying other neurocognitive diseases without encephalitis. The simian immunodeficiency virus (SIV)-infected rhesus macaque model is instrumental in studying the effects of opioid abuse on PLWH due to its similarity to HIV infection. The review highlights the importance of using non-human primate models to study the comorbidity of opioid abuse and HIV infection. It also emphasizes the need to consider modifiable risk factors such as gut homeostasis and pulmonary pathogenesis associated with SIV infection and opioid abuse in this model. Moreover, the review suggests that these non-human primate models can also be used in developing effective treatment strategies for NeuroHIV and opioid addiction. Therefore, non-human primate models can significantly contribute to understanding the complex interplay between HIV infection, opioid abuse, and associated comorbidities.

Varicella-zoster virus (VZV) infection may cause vascular inflammatory changes leading to an increased risk of stroke. Previous studies have focused on the risk of stroke and less on changes in stroke risk and prognosis. We aimed to explore the changing patterns of stroke risk and stroke prognosis after VZV infection. This study is a systematic review and meta-analysis. We searched PubMed, Embase, and the Cochrane Library for studies on stroke after VZV infection between January 1, 2000, and October 5, 2022. Relative risks were combined for the same study subgroups using a fixed-effects model and pooled across studies using a random-effects model. 27 studies met the requirements, including 17 herpes zoster (HZ) studies and ten chickenpox studies. There was an increased risk of stroke after HZ, and this risk decreased over time: relative risk 1.80 (95% CI 1.42-2.29) within 14 days, 1.61 (95% CI 1.43-1.81) within 30 days, 1.45 (95% CI 1.33-1.58) within 90 days, 1.32 (95% CI 1.25-1.39) within 180 days, 1.27 (95% CI 1.15-1.40) at one year and 1.19 (95% CI 0.90-1.59) after one year, with the same trend in the stroke subtype. The risk of stroke after herpes zoster ophthalmicus was higher, with a maximum relative risk of 2.26 (95% CI 1.35-3.78). The risk of stroke after HZ was higher in patients aged around 40 years: relative risk 2.53 (95% CI 1.59-4.02), and similar in men and women. Also, after pooling studies of post-chickenpox stroke, we found that the middle cerebral artery and its branches were most frequently involved (78.2%), with a better prognosis in most patients (83.1%) and less frequent vascular persistence progression (8.9%). In conclusion, the risk of stroke increases after VZV infection, decreasing over time. Post-infection vascular inflammatory changes often occur in the middle cerebral artery and its branches, with a better prognosis in most patients and less frequent persistent progression.

NOTCH receptors are relevant to multiple neurodegenerative diseases. However, the roles and mechanisms of NOTCH receptors in HIV-associated neurocognitive disorder (HAND) remain largely unclear. Transactivator of transcription (Tat) induces oxidative stress and inflammatory response in astrocytes, thereby leading to neuronal apoptosis in the central nervous system. We determined that NOTCH3 expression was upregulated during subtype B or C Tat expression in HEB astroglial cells. Moreover, bioinformatics analysis of the Gene Expression Omnibus (GEO) dataset revealed that NOTCH3 mRNA expression in the frontal cortex tissues of HIV encephalitis patients was higher than that of HIV control patients. Of note, subtype B Tat, rather than subtype C Tat, interacted with the extracellular domain of the NOTCH3 receptor, thus activating NOTCH3 signaling. Downregulation of NOTCH3 attenuated subtype B Tat-induced oxidative stress and reactive oxygen species generation. In addition, we demonstrated that NOTCH3 signaling facilitated subtype B Tat-activated NF-κB signaling pathway, thereby mediating pro-inflammatory cytokines IL-6 and TNF-α production. Furthermore, downregulation of NOTCH3 in HEB astroglial cells protected SH-SY5Y neuronal cells from astrocyte-mediated subtype B Tat neurotoxicity. Taken together, our study clarifies the potential role of NOTCH3 in subtype B Tat-induced oxidative stress and inflammatory response in astrocytes, which could be a novel therapeutic target for the relief of HAND.

Human immunodeficiency virus (HIV), the main contributor of the ongoing AIDS epidemic, remains one of the most challenging and complex viruses to target and eradicate due to frequent genome mutation and immune evasion. Despite the development of potent antiretroviral therapies, HIV remains an incurable infection as the virus persists in latent reservoirs throughout the body. To innovate a safe and effective cure strategy for HIV in humans, animal models are needed to better understand viral proliferation, disease progression, and therapeutic response. Nonhuman primates infected with simian immunodeficiency virus (SIV) provide an ideal model to study HIV infection and pathogenesis as they are closely related to humans genetically and express phenotypically similar immune systems. Examining the clinical outcomes of novel treatment strategies within nonhuman primates facilitates our understanding of HIV latency and advances the development of a true cure to HIV.