Zika virus (ZIKV) is a mosquito-borne flavivirus that causes systemic infection with the neurotropic potential. Accordingly, it is a pathogen of significant public health concern worldwide, especially in the Americas. Although most infections are asymptomatic, a small percentage of patients experience complications, such as congenital anomalies in the developing fetus of pregnant women infected with the virus. MicroRNAs (miRNAs), a class of small non-coding RNAs, play crucial roles in regulating cellular signaling pathways and physiological processes. Alterations in miRNA expression have been linked to various disease mechanisms, including those triggered by viral infections. Although substantial progress has been made in understanding ZIKV-host interactions since the 2015–2016 outbreaks, a more comprehensive understanding of the molecular mechanisms involved is still needed. In conclusion, The reviewed evidence suggests multiple dysregulated host miRNAs and mRNAs upon ZIKV infection, which have roles in neurodevelopment. A more comprehensive understanding of dysregulated miRNAs in viral infections may enhance the identification, prevention, and treatment of diseases.
Varicella zoster virus (VZV) reactivation has emerged as a potential contributor to dementia through vascular and inflammatory mechanisms, with herpes zoster ophthalmicus (HZO) representing a potentially higher-risk phenotype because of its association with cerebrovascular complications. This narrative review evaluated the epidemiological and mechanistic evidence linking VZV reactivation to cognitive decline. MEDLINE, PubMed, Embase, and the Cochrane Library were searched from inception to March 2026, supplemented by relevant publications identified during revision through October 2026, with emphasis on systematic reviews, large observational studies, quasi-experimental vaccination studies, and mechanistic investigations. Infection-based studies demonstrated heterogeneous findings, with modest associations between herpes zoster and subsequent dementia that frequently attenuated after adjustment for frailty and comorbidity. In contrast, vaccination studies, particularly natural experiments and quasi-experimental analyses, consistently reported lower dementia incidence following zoster immunisation, although causal interpretation and the magnitude of any protective effect remain uncertain. Observational studies suggest that antiviral therapy is associated with fewer short-term cerebrovascular complications, although its relationship with long-term cognitive outcomes remains uncertain. VZV-associated vasculopathy provides the strongest mechanistic rationale for a link with cognitive decline, whereas neuroinflammation, possible blood-brain barrier dysfunction, and interactions with neurodegenerative processes remain proposed pathways. Current evidence suggests that VZV reactivation may accelerate cognitive decline in susceptible individuals, but causality remains unproven. Further prospective studies are needed to clarify the contribution of VZV reactivation and the potential neuroprotective effects of vaccination and antiviral therapy.
Toxic cytoplasmic aggregates containing the nuclear RNA-binding protein TDP-43 form in several neurodegenerative diseases; however, the molecular triggers driving aggregation remain unclear. Epidemiological evidence has linked latent and reactivating herpes simplex virus type-1 (HSV-1) infections to neurodegenerative disease onset, but it is unknown if HSV-1 infection impacts TDP-43 subcellular distribution. Here, we demonstrate that HSV-1 infection of epithelial cells and DRG-derived neurons results in nuclear TDP-43 redistribution and TDP-43 accumulation within distinct nuclear assemblies. Cytoplasmic TDP-43 was not detected under these conditions. Nuclear TDP-43 assembly occurred early in infection and was dependent upon expression of the critical ICP0 regulatory gene. Remarkably, ectopic ICP0 expression in uninfected cells was sufficient for nuclear TDP-43 assembly. Thus, expression of a single viral gene product encoded by a near ubiquitous human herpesvirus can alter TDP-43 nuclear localization. Moreover, our work identifies a potential mechanistic link between herpesvirus infection and neuronal disease factor mislocalization.
Multiple sclerosis (MS) prevalence has increased to medium-to-high levels in several countries of the Middle East and North Africa (MENA), while Epstein–Barr virus (EBV) exposure as one of the most consistently reported MS risk factors is common throughout the region. This systematic review and meta-analysis descriptively mapped published estimates of MS prevalence and EBV seroprevalence alongside each other in MENA countries. We searched MEDLINE, PubMed, Embase, Scopus, and Web of Science until 18 June 2022. Observational studies reporting MS prevalence or EBV seroprevalence among healthy MENA populations were eligible. For quantitative EBV synthesis, we restricted analyses to studies reporting VCA-IgG seroprevalence to improve comparability across studies. Studies reporting the prevalence of specific type of MS or those assessing EBV infection by IgA antibodies or non-serological tissues or without a control arm representing general population were excluded. The Joanna Briggs Institute (JBI) critical appraisal tools were used to determine the quality of the studies. The heterogeneity of studies was evaluated using I2 statistics. Results of the fix-effects meta-analysis were presented using prevalence and 95
Encephalitis guidelines recommend repeating a lumbar puncture (LP) 3–7 days after an initial negative cerebrospinal fluid (CSF) herpes simplex virus (HSV) polymerase chain reaction (PCR) test in patients with high suspicion for HSV or varicella zoster virus (VZV), but this subgroup has not been specified. Retrospective observational study of 602 adults with encephalitis from 2002 to 2023 from two large U.S. healthcare systems. Multivariate logistic regression models were developed and internally validated to identify clinically relevant and statistically significant features predicting HSV, VZV, and combined HSV/VZV encephalitis. HSV and VZV encephalitis were diagnosed in 103 (17.1
