Assembly of mature herpesvirus particles is associated with extensive rearrangement of cytoplasmic membranes. Herpes simplex virus type 1 (HSV-1) infection in neuronal cells induces the formation of a distinctive cytoplasmic viral assembly compartment (cVAC), in which rearranged host membranes and viral proteins are clustered at the perinuclear microtubule-organizing center (MTOC). Although both the trans-Golgi network (TGN) and endosomal compartments have been implicated as membrane sources for cytoplasmic envelopment, how secretory and endosomal pathways are reorganized and associated within the cVAC remains unclear. Here, we treated HSV-1-infected cells with nocodazole at a post-entry stage to disperse membrane components of the cVAC and identify microtubule-independent membrane organizations and associations using immunofluorescence imaging. We found that the Golgi apparatus was fragmented during infection but maintained cisternal stacking, as the Golgi markers GM130, GalT, and GRASP65 remained colocalized in both the absence and presence of nocodazole. We further demonstrated that Golgi mini-stacks retained their association with Rab6 during HSV-1 infection and formed microtubule-independent associations with early and recycling endosomes, resulting in the formation of Golgi-endosome super-mini-stacks. Viral capsid, glycoprotein, and tegument proteins were colocalized with Golgi-endosome super-mini-stacks in both the presence and absence of microtubules, suggesting that this membrane complex serves as a site of cytoplasmic envelopment regardless of clustering at the MTOC. Formation of these stable Golgi-endosome associations did not require viral capsids. Neither actin filaments nor acetylated microtubules colocalized with Golgi-endosome super-mini-stacks, suggesting that cytoskeletal elements are not required for this association.IMPORTANCEMany viruses remodel host cytoplasmic membranes to facilitate their assembly. Elucidating the molecular mechanisms underlying this remodeling may reveal novel antiviral targets while also providing insight into fundamental principles of intracellular membrane organization. Infection with an important human pathogen, herpes simplex virus type 1 (HSV-1), induces extensive membrane remodeling that leads to the formation of the cytoplasmic viral assembly compartment (cVAC) in neuronal cells, yet the underlying mechanisms remain poorly understood. Here, we demonstrate that HSV-1 induces stable associations between membranes within the cVAC. Our findings support a model in which HSV-1 generates a dynamic hybrid membrane compartment during infection, potentially reconciling conflicting views on the roles of distinct membrane sources in cytoplasmic assembly.

A 63-year-old male with a history of untreated HIV presented to the emergency room with acute on chronic watery diarrhea, weight loss, fatigue, fever and chills. His vital signs were within normal limits and his abdomen was soft, nondistended and tender to palpation in 4 quadrants without peritonitis. He did not have leukocytosis on presentation. CD4 count was 310. CT scan showed inflammatory changes in the rectum and sigmoid colon. Comprehensive infectious workup was negative for any pathogens including cytomegalovirus (CMV), cryptosporidium, chlamydia, gonorrhea, C. difficile, cryptococcus, tuberculosis (TB) and herpes simplex virus (HSV). Colonoscopy was performed and showed a continuous area of nonbleeding ulcerated mucosa in the rectum, sigmoid, descending and transverse colon (Fig. 1). Pancolonic biopsies revealed active colitis with focal areas of basal plasmacytosis and crypt branching in left colon, suggestive of acute on chronic colitis and possible ulcerative colitis (UC). Gastroenterology and infectious disease were consulted and patient was started on IV methylprednisolone for presumed UC flare. Over the next few weeks, the patient proceeded to develop melena as well as increased lower abdominal and pelvic pain with intermittent fevers despite IV steroid treatment. The patient was trialed on IV infliximab also without significant improvement. After several weeks of steroid and biologic treatment, he developed increased abdominal pain with tachycardia and hemodynamic instability. His examination was significant for peritonitis with abdominal distension concerning for fulminant colitis. Colorectal surgery was consulted and proceeded to do an emergent total abdominal colectomy and end ileostomy. Intraoperatively he was found to have a small anterior distal rectal perforation. The decision was made to drain this area widely with rectal drain and fecal diversion and start him on IV antibiotic therapy. His final pathology from the index operation showed ulceration and acute colitis. There was no chronic crypt architectural distortion such as crypt dropout, disarray, crypt branching or basal plasmacytosis that are often seen in inflammatory bowel disease (IBD). There was also increased apoptotic bodies and mitoses that were not consistent with IBD. After reviewing the clinical presentation, his disease progression, and final pathology, the treating team diagnosed the patient with HIV-associated colitis.

Herpes simplex virus type 2 (HSV-2) is a widely prevalent human pathogen responsible for the majority of genital herpes infections. Type-specific serological screening is a valuable approach for identifying asymptomatic individuals who may unknowingly transmit HSV to sexual partners and neonates, and can inform prevention, treatment, and vaccination strategies aimed at reducing transmission. Here, we describe the development and preliminary evaluation of a Europium nanoparticle-based lateral flow assay (EuNP-LFA) for rapid detection of HSV-2-specific immunoglobulin G (IgG) antibodies in human serum within 10 minutes. Preliminary performance evaluation using a commercially available anti-herpes mixed-titer performance panel demonstrated 90% sensitivity and 90.9% specificity relative to the FDA-cleared HerpeSelect™ HSV-2 ELISA reference classification. Receiver operating characteristic analysis yielded an area under the curve of 0.918 (95% CI: 0.688-0.983), indicating good discriminatory performance in this preliminary dataset. These findings support the feasibility of the EuNP-LFA as a proof-of-concept platform for rapid HSV-2 serological testing and support further evaluation in larger, clinically representative specimen populations to establish its diagnostic performance and potential utility for point-of-care applications.

Herpes simplex encephalitis (HSE), caused by herpes simplex virus type 1 (HSV-1), is the most common cause of sporadic viral encephalitis and remains associated with substantial mortality and long-term neurological morbidity despite effective antiviral therapy. Although HSE is classically characterized by involvement of the medial temporal lobes and limbic system, recent clinical, preclinical and neuroimaging studies highlight involvement of prefrontal cortical regions, including the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC). The functional consequences of HSV-1 associated injury may be particularly relevant to the persistent executive, cognitive, motivational, emotional, and behavioral abnormalities observed in HSE survivors. However, the mechanisms linking HSV-1 infection to prefrontal injury and subsequent neurobehavioral dysfunction remain incompletely defined. This review examines HSV-1 neuropathogenesis through a prefrontal cortical framework, with a focus on the mPFC and OFC, and evaluates potential mechanisms underlying their vulnerability. Current evidence supports a multistep hypothesis for HSV-1-associated injury involving olfactory and trigeminal neural entry, microtubule-dependent axonal transport, dissemination, and potential regional differences in cellular susceptibility. Further, we highlight cellular mechanisms of HSV-1-associated injury, including microglial and NLRP3 inflammasome activation, astrocytic dysfunction, neurovascular unit disruption, neuronal and synaptic injury, and viral immune-evasion mechanisms that facilitate viral persistence and amplify host-mediated injury. Lastly, we integrate these mechanisms with the functional organization of prefrontal-frontal-limbic networks to consider how regional injury may contribute to persistent cognitive and behavioral dysfunction following HSE. The studies discussed here provide a framework for linking HSV-1-associated prefrontal injury to long-lasting cognitive and behavioral sequelae of HSE, while highlighting critical gaps in our understanding of these HSV-driven mechanisms.

The Herpes Simplex Virus 1 (HSV-1) genome undergoes extensive chromatinization following entry into the nucleus, yet how viral regulatory elements influence this process during lytic infection remains poorly understood. The HSV-1 latency-associated transcript enhancer (LTE) is well established as a key element in the regulation of latency and reactivation, but its role during the productive infection has not been defined. Here, we identify a role for the LTE in regulating chromatin composition on the lytic HSV-1 genome. Deletion of a 310-bp region within the LTE selectively reduced enrichment of the canonical histone H3.1 at specific viral lytic genes, including ICP4 and ICP8, without altering H3.3 enrichment. This phenotype was not reproduced using a second LTE deletion that disrupted enhancer activity, indicating that regulation of H3.1 enrichment is separable from the function of the enhancer. LTE-dependent H3.1 enrichment persisted in the absence of viral DNA replication and was accompanied by reduced occupancy of the H3.1 histone chaperone CAF-1. However, depletion of CAF-1 did not substantially reduce H3.1 enrichment, indicating that additional mechanisms contribute to H3.1 association with the viral genome. Together, these findings reveal that the HSV-1 LTE regulates locus-specific chromatin composition during early lytic infection and identify a previously unrecognized connection between a viral enhancer and histone H3.1 enrichment on the incoming viral genome.

TAR DNA-binding protein-43 (TDP-43) alterations are a key hallmark of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative disorders. Increasing evidence links these conditions to viral infections, but it is not known if and how viral pathogens may be affected by disease-associated TDP-43. We found that ALS/FTD-linked forms of human TDP-43 prevent infection by herpes simplex virus type-1 (HSV-1), a common neurotropic virus. This cell-autonomous protective effect was conserved across different TDP-43 mutations, sporadic ALS, and C9ORF72 -ALS, in neural and non-neural cell types, and in patient-derived cells and animal models. In addition to restricting infection, TDP-43 mutation prevented inflammatory and cell stress-related responses to HSV-1 exposure. TDP-43 knockdown but not overexpression was sufficient to protect cells from HSV-1 infection, implicating a loss-of-function mechanism. Neurons with TDP-43 mutation had disruptions in adhesion-related pathways and, accordingly, had reduced early-stage viral binding and entry. Further analyses revealed alternative RNA splicing and impairment of focal adhesion kinase (FAK/PTK2), a key mediator of cell-adhesion pathways. Inhibition of FAK was sufficient to decrease HSV-1 infection, and genetic enhancement of functional but not inactive FAK promoted infectivity in cells with TDP-43 mutation. Together, these data indicate that TDP-43 affects virus-host interactions by influencing adhesion pathways required for viral infection.

Human herpesviruses (HHV) remain latent after primary infection and may reactivate during critical illness. HHV reactivation has been associated with adverse clinical outcomes, yet its pathogenic significance and optimal management remain unclear. This review summarizes the dysregulated immune mechanisms and risk factors for HHV reactivation in critical illness, treatment options, outcomes, current diagnostic challenges, and emerging precision medicine approaches. Critical illness induces profound immune dysregulation characterized by an initial hyperinflammatory response followed by immunosuppression, T-cell exhaustion, impaired natural killer cell function, and disrupted antiviral surveillance. These changes facilitate reactivation of latent HHV, including herpes simplex virus type 1 (HSV-1), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV-6). HSV and CMV reactivation in mechanically ventilated and septic patients have been associated with prolonged mechanical ventilation, longer intensive care unit (ICU) stay, secondary infections, and increased mortality. However, the distinction between clinically significant disease from asymptomatic reactivation remains challenging. Current evidence does not support routine antiviral prophylaxis in immunocompetent ICU patients. Emerging approaches including metagenomic next-generation sequencing, host transcriptomics, immune phenotyping, and multi-omics integration may improve risk stratification and identify patient subgroups that are most likely to benefit from targeted intervention. HHV reactivation may serve as a biomarker and potential mediator of adverse outcomes. Improved understanding of host-virus interactions, coupled with precision medicine that integrates virological and immunological data, is required to differentiate clinically relevant reactivation from epiphenomena and to guide individualized therapeutic strategies.

CO2 sorbents play a central role in many carbon capture technologies. Visual monitoring of the sorbent behavior during CO2 capture could provide direct feedback and enable the optimization of both the sorbent and the reactor, which remains largely unexplored. In this work, we develop a self-reporting CO2 sorbent, prove its quantitative indication of CO2 absorption and desorption, and apply this method to evaluate different methods of sorbent regeneration. A pH indicator, thymol blue (TB), was embedded into polyethyleneimine (PEI) hydrogel particles, revealing a clear color transition from blue to green, yellow, and orange during CO2 absorption. This optical response was quantified by extracting Hue, a color coordinate in the Hue, Saturation, Value (HSV) space, from the particle images. Time-resolved analysis of the CO2 absorption revealed that Hue closely follows the measured CO2 uptake. A previously developed diffusion-reaction model was employed to investigate the relationship between the optical response and the internal chemistry of the particles. The measured Hue evolution more closely follows the modeled protonation response averaged over a substantial fraction of the particle volume than that of the shallow near-surface regions, supporting its potential use as an optical indicator for CO2 uptake. The robustness of the optical response was further confirmed by evaluating particles with different water contents, and excellent reversibility of the optical response was demonstrated during steam regeneration. As a final step, microwave regeneration was optically evaluated via this method, and shown to be much faster but less complete than steam regeneration. These results demonstrate that PEI/TB hydrogel particles can provide a timely, direct, and convenient optical signal during CO2 absorption and regeneration, enabling pathways for optimization at particle and potentially reactor scales.

A DFT-assisted Raman framework integrating difference-derivative-PCA highly distinguishable Raman bands screening and difference visualization (DD-PCA-HSV), characteristic peak correlation analysis, and machine learning classification was developed for three milled rice types (SXJ-100, FYXZ, and BJR) from the Taihu Lake Basin. Five independent lots were analyzed for each type. Lots L1-L4 formed the development dataset, and L5 was reserved for independent testing. DFT calculations on simplified amylose and amylopectin models, together with literature, supported the assignment of 22 characteristic Raman peaks. Grouped four-fold cross-validation of DD-PCA-HSV on L1-L4 reproducibly retained six bands at 439, 576, 939, 1126, 1262, and 1460 cm[-1]. Z scores of these bands characterized spectral differences among the three rice types in the development dataset, and the same relative trends were reproduced in L5. Differences between BJR and SXJ-100/FYXZ were mainly associated with pyranose-ring and glycosidic-linkage vibrations, whereas differences between SXJ-100 and FYXZ were mainly associated with CO and CCO stretching vibrations. Linear correlation analysis combined with a dual-threshold rule identified 1080/1106 and 524/615 cm[-1] as discriminative peak pairs. Subsampling analysis indicated that 30 spectra were sufficient for repeatable R[2] estimation. The corresponding linear correlation features were reproduced in L5. Among RF, DT, and SVM models, SVM using normalized spectra achieved the best independent test performance, with accuracy, macro-precision, macro-recall, and macro-F1 all reaching 0.98. Overall, the framework distinguished the investigated rice types while linking discriminative Raman features to molecular vibrations, thereby providing a chemically interpretable basis for Raman-based rice characterization.

Pseudorabies virus (PRV), an important member of the Alphaherpesvirinae subfamily, shares high evolutionary homology with other members of the same subfamily, including human herpes simplex virus (HSV) and varicella-zoster virus (VZV). However, significant differences exist among them in terms of host range, pathogenicity, and immune evasion strategies. This review systematically compares the roles of PRV, HSV type 1 (HSV-1), and VZV in modulating host innate immune responses, encompassing the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling, RIG-I-like receptor (RLR) signaling, NOD-like receptor (NLR) signaling, Toll-like receptor (TLR) signaling, Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, apoptosis, and autophagy. By summarizing and comparing the interactions of these three viruses with the host innate immune response, this review aims to provide a theoretical reference for understanding the conserved and unique mechanisms of immune evasion among alphaherpesviruses, and to offer insights for the development of novel antiviral strategies.

Exposure to environmental risk factors has been considered a major contributor to neurodegenerative diseases. As biological factors, infectious pathogens pose health concerns in the development of numerous aging-associated neurological defects. Emerging evidence continuously demonstrates the association between viral infection and the deterioration of brain function, such as dementia, multiple sclerosis, and microcephaly in infants. As intracellular pathogens, viruses demand macromolecules and energy by hijacking the host cell and reprogramming cellular metabolism. This study focuses on alterations in lipid metabolism in virus-infected neuronal cells using the DNA virus HSV-1 and the RNA virus ZIKV. We found that both HSV-1 and ZIKV downregulate lipid metabolism, sphingolipid metabolism, glycerophospholipid, and plasmalogen pathways in iPSC-derived neuronal cells, which may contribute to the pathogenesis of neurological diseases. The metabolomic dataset and analysis results will provide a valuable reference in studying the role of viral infection in neurodegeneration in vitro and in vivo .