Elongation enhances encounter rates between phytoplankton in turbulence.

Phytoplankton come in a stunning variety of shapes but elongated morphologies dominate-typically 50% of species have aspect ratio above 5, and bloom-forming species often form chains whose aspect ratios can exceed 100. How elongation affects encounter rates between phytoplankton in turbulence has remained unknown, yet encounters control the formation of marine snow in the ocean. Here, we present simulations of encounters among elongated phytoplankton in turbulence, showing that encounter rates between neutrally buoyant elongated cells are up to 10-fold higher than for spherical cells and even higher when cells sink. Consequently, we predict that elongation can significantly speed up the formation of marine snow compared to spherical cells. This unexpectedly large effect of morphology in driving encounter rates among plankton provides a potential mechanistic explanation for the rapid clearance of many phytoplankton blooms.

Quantitative Prediction of Sling Events in Turbulence at High Reynolds Numbers.

Collisional growth of droplets, such as occurring in warm clouds, is known to be significantly enhanced by turbulence. Whether particles collide depends on their flow history, in particular on their encounters with highly intermittent small-scale turbulent structures, which despite their rarity can dominate the overall collision rate. Here, we develop a quantitative criterion for sling events based on the velocity gradient history along particle paths. We show by a combination of theory and simulations that the problem reduces to a one-dimensional localization problem as encountered in condensed matter physics. The reduction demonstrates that the creation of slings is controlled by the minimal real eigenvalue of the velocity gradient tensor. We use fully resolved turbulence simulations to confirm our predictions and study their Stokes and Reynolds number dependence. We also discuss extrapolations to the parameter range relevant for typical cloud droplets, showing that sling events at high Reynolds numbers are enhanced by an order of magnitude for small Stokes numbers. Thus, intermittency could be a significant ingredient in the collisional growth of rain droplets.

GRK2 mediates ß-arrestin interactions with 5-HT2 receptors for JC polyomavirus endocytosis.

JC polyomavirus (JCPyV) infects the majority of the population, establishing a lifelong, asymptomatic infection in the kidney of healthy individuals. People that become severely immunocompromised may experience JCPyV reactivation, which can cause progressive multifocal leukoencephalopathy (PML), a neurodegenerative disease. Due to a lack of therapeutic options, PML results in fatality or significant debilitation among affected individuals. Cellular internalization of JCPyV is mediated by serotonin 5-hydroxytryptamine subfamily 2 receptors (5-HT2Rs) via clathrin-mediated endocytosis. The JCPyV entry process requires the clathrin-scaffolding proteins ß-arrestin, adaptor protein 2 (AP2), and dynamin. Further, a ß-arrestin interacting domain, the Ala-Ser-Lys (ASK) motif, within the C-terminus of 5-HT2AR is important for JCPyV internalization and infection. Interestingly, 5-HT2R subtypes A, B, and C equally support JCPyV entry and infection, and all subtypes contain an ASK motif, suggesting a conserved mechanism for viral entry. However, the role of the 5-HT2R ASK motifs and the activation of ß-arrestin-associated proteins during internalization has not been fully elucidated. Through mutagenesis, the ASK motifs within 5-HT2BR and 5-HT2CR were identified as critical for JCPyV internalization and infectivity. Further, utilizing biochemical pulldown techniques, mutagenesis of the ASK motifs in 5-HT2BR and 5-HT2CR resulted in reduced ß-arrestin binding. Utilizing small-molecule chemical inhibitors and RNA interference, G-protein receptor kinase 2 (GRK2) was determined to be required for JCPyV internalization and infection by mediating interactions between ß-arrestin and the ASK motif of 5-HT2Rs. These findings demonstrate that GRK2 and ß-arrestin interactions with 5-HT2Rs are critical for JCPyV entry by clathrin-mediated endocytosis and resultant infection.IMPORTANCE As intracellular parasites, viruses require a host cell to replicate and cause disease. Therefore, virus-host interactions contribute to viral pathogenesis. JC polyomavirus (JCPyV) infects most of the population, establishing a lifelong asymptomatic infection within the kidney. Under conditions of severe immunosuppression JCPyV may spread to the central nervous system, causing the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). Individuals living with HIV or undergoing immunomodulatory therapies are at risk for developing PML. The mechanisms of how JCPyV uses specific receptors on the surface of host cells to initiate internalization and infection is a poorly understood process. We have further identified cellular proteins involved in JCPyV internalization and infection and elucidated their specific interactions that are responsible for activation of receptors. Collectively, these findings illuminate how viruses usurp cellular receptors during infection, contributing to current development efforts for therapeutic options for the treatment or prevention of PML.

Rearrangement in the Hypervariable Region of JC Polyomavirus Genomes Isolated from Patient Samples and Impact on Transcription Factor-Binding Sites and Disease Outcomes.

JC polyomavirus (JCPyV) is the causative agent of the fatal, incurable, neurological disease, progressive multifocal leukoencephalopathy (PML). The virus is present in most of the adult population as a persistent, asymptotic infection in the kidneys. During immunosuppression, JCPyV reactivates and invades the central nervous system. A main predictor of disease outcome is determined by mutations within the hypervariable region of the viral genome. In patients with PML, JCPyV undergoes genetic rearrangements in the noncoding control region (NCCR). The outcome of these rearrangements influences transcription factor binding to the NCCR, orchestrating viral gene transcription. This study examines 989 NCCR sequences from patient isolates deposited in GenBank to determine the frequency of mutations based on patient isolation site and disease status. The transcription factor binding sites (TFBS) were also analyzed to understand how these rearrangements could influence viral transcription. It was determined that the number of TFBS was significantly higher in PML samples compared to non-PML samples. Additionally, TFBS that could promote JCPyV infection were more prevalent in samples isolated from the cerebrospinal fluid compared to other locations. Collectively, this research describes the extent of mutations in the NCCR that alter TFBS and how they correlate with disease outcome.

JC Polyomavirus Infection Reveals Delayed Progression of the Infectious Cycle in Normal Human Astrocytes.

JC polyomavirus (JCPyV) infects 50 to 80% of the population and is the causative agent of a fatal demyelinating disease of the central nervous system (CNS). JCPyV presents initially as a persistent infection in the kidneys of healthy people, but during immunosuppression, the virus can reactivate and cause progressive multifocal leukoencephalopathy (PML). Within the CNS, JCPyV predominately targets two cell types, oligodendrocytes and astrocytes. Until recently, the role of astrocytes has been masked by the pathology in the myelin-producing oligodendrocytes, which are lytically destroyed by the virus. To better understand how astrocytes are impacted during JCPyV infection, the temporal regulation and infectious cycle of JCPyV were analyzed in primary normal human astrocytes (NHAs). Previous research to define the molecular mechanisms underlying JCPyV infection has mostly relied on the use of cell culture models, such as SVG-A cells (SVGAs), an immortalized, mixed population of glial cells transformed with simian virus 40 (SV40) T antigen. However, SVGAs present several limitations due to their immortalized characteristics, and NHAs represent an innovative approach to study JCPyV infection in vitro Using infectivity assays, quantitative PCR, and immunofluorescence assay approaches, we have further characterized JCPyV infectivity in NHAs. The JCPyV infectious cycle is significantly delayed in NHAs, and the expression of SV40 T antigen alters the cellular environment, which impacts viral infection in immortalized cells. This research establishes a foundation for the use of primary NHAs in future studies and will help unravel the role of astrocytes in PML pathogenesis.IMPORTANCE Animal models are crucial in advancing biomedical research and defining the pathogenesis of human disease. Unfortunately, not all diseases can be easily modeled in a nonhuman host or such models are cost prohibitive to generate, including models for the human-specific virus JC polyomavirus (JCPyV). JCPyV infects most of the population but can cause a rare, fatal disease, progressive multifocal leukoencephalopathy (PML). There have been considerable advancements in understanding the molecular mechanisms of JCPyV infection, but this has mostly been limited to immortalized cell culture models. In contrast, PML pathogenesis research has been greatly hindered because of the lack of an animal model. We have further characterized JCPyV infection in primary human astrocytes to better define the infectious process in a primary cell type. Albeit a cell culture model, primary astrocytes may better recapitulate human disease, are easier to maintain than other primary cells, and are less expensive than using an animal model.

Role of Advective Inertia in Active Nematic Turbulence.

Suspensions of active agents with nematic interactions exhibit complex spatiotemporal dynamics such as mesoscale turbulence. Since the Reynolds number of microscopic flows is very small on the scale of individual agents, inertial effects are typically excluded in continuum theories of active nematic turbulence. Whether active stresses can collectively excite inertial flows is currently unclear. To address this question, we investigate a two-dimensional continuum theory for active nematic turbulence. In particular, we compare mesoscale turbulence with and without the effects of advective inertia. We find that inertial effects can influence the flow already close to the onset of the turbulent state and, moreover, give rise to large-scale fluid motion for strong active driving. A detailed analysis of the kinetic energy budget reveals an energy transfer to large scales mediated by inertial advection. While this transfer is small in comparison to energy injection and dissipation, its effects accumulate over time. The inclusion of friction, which is typically present in experiments, can compensate for this effect. The findings suggest that the inclusion of inertia and friction may be necessary for dynamically consistent theories of active nematic turbulence.

Emergence of phytoplankton patchiness at small scales in mild turbulence.

Phytoplankton often encounter turbulence in their habitat. As most toxic phytoplankton species are motile, resolving the interplay of motility and turbulence has fundamental repercussions on our understanding of their own ecology and of the entire ecosystems they inhabit. The spatial distribution of motile phytoplankton cells exhibits patchiness at distances of decimeter to millimeter scales for numerous species with different motility strategies. The explanation of this general phenomenon remains challenging. Furthermore, hydrodynamic cell-cell interactions, which grow more relevant as the density in the patches increases, have been so far ignored. Here, we combine particle simulations and continuum theory to study the emergence of patchiness in motile microorganisms in three dimensions. By addressing the combined effects of motility, cell-cell interaction, and turbulent flow conditions, we uncover a general mechanism: The coupling of cell-cell interactions to the turbulent dynamics favors the formation of dense patches. Identification of the important length and time scales, independent from the motility mode, allows us to elucidate a general physical mechanism underpinning the emergence of patchiness. Our results shed light on the dynamical characteristics necessary for the formation of patchiness and complement current efforts to unravel planktonic ecological interactions.

Capturing Velocity Gradients and Particle Rotation Rates in Turbulence.

Turbulent fluid flows exhibit a complex small-scale structure with frequently occurring extreme velocity gradients. Particles probing such swirling and straining regions respond with an intricate shape-dependent orientational dynamics, which sensitively depends on the particle history. Here, we systematically develop a reduced-order model for the small-scale dynamics of turbulence, which captures the velocity gradient statistics along particle paths. An analysis of the resulting stochastic dynamical system allows pinpointing the emergence of non-Gaussian statistics and nontrivial temporal correlations of vorticity and strain, as previously reported from experiments and simulations. Based on these insights, we use our model to predict the orientational statistics of anisotropic particles in turbulence, enabling a host of modeling applications for complex particulate flows.

ERK Is a Critical Regulator of JC Polyomavirus Infection.

The human JC polyomavirus (JCPyV) infects the majority of the population worldwide and presents as an asymptomatic, persistent infection in the kidneys. In individuals who are immunocompromised, JCPyV can become reactivated and cause a lytic infection in the central nervous system resulting in the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML). Infection is initiated by interactions between the capsid protein viral protein 1 (VP1) and the α2,6-linked sialic acid on lactoseries tetrasaccharide c (LSTc), while JCPyV internalization is facilitated by 5-hydroxytryptamine 2 receptors (5-HT2Rs). The mechanisms by which the serotonin receptors mediate virus entry and the signaling cascades required to drive viral infection remain poorly understood. JCPyV was previously shown to induce phosphorylation of extracellular signal-regulated kinase (ERK), a downstream target of the mitogen-activated protein kinase (MAPK) pathway, upon virus entry. However, it remained unclear whether ERK activation was required for JCPyV infection. Both ERK-specific small interfering RNA (siRNA) and ERK inhibitor treatments resulted in significantly diminished JCPyV infection in both kidney and glial cells yet had no effect on the infectivity of the polyomavirus simian virus 40 (SV40). Experiments characterizing the role of ERK during steps in the viral life cycle indicate that ERK activation is required for viral transcription, as demonstrated by a significant reduction in production of large T antigen (TAg), a key viral protein associated with the initiation of viral transcription and viral replication. These findings delineate the role of the MAPK-ERK signaling pathway in JCPyV infection, elucidating how the virus reprograms the host cell to promote viral pathogenesis.IMPORTANCE Viral infection is dependent upon host cell factors, including the activation of cellular signaling pathways. These interactions between viruses and host cells are necessary for infection and play an important role in viral disease outcomes. The focus of this study was to determine how the human JC polyomavirus (JCPyV), a virus that resides in the kidney of the majority of the population and can cause the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML) in the brains of immunosuppressed individuals, usurps a cellular signaling pathway to promote its own infectious life cycle. We demonstrated that the activation of extracellular signal-regulated kinase (ERK), a component of the mitogen-activated protein kinase (MAPK) pathway, promotes JCPyV transcription, which is required for viral infection. Our findings demonstrate that the MAPK-ERK signaling pathway is a key determinant of JCPyV infection, elucidating new information regarding the signal reprogramming of host cells by a pathogenic virus.

Large-Scale Pattern Formation in the Presence of Small-Scale Random Advection.

Despite the presence of strong fluctuations, many turbulent systems such as Rayleigh-Bénard convection and Taylor-Couette flow display self-organized large-scale flow patterns. How do small-scale turbulent fluctuations impact the emergence and stability of such large-scale flow patterns? Here, we approach this question conceptually by investigating a class of pattern forming systems in the presence of random advection by a Kraichnan-Kazantsev velocity field. Combining tools from pattern formation with statistical theory and simulations, we show that random advection shifts the onset and the wave number of emergent patterns. As a simple model for pattern formation in convection, the effects are demonstrated with a generalized Swift-Hohenberg equation including random advection. We also discuss the implications of our results for the large-scale flow of turbulent Rayleigh-Bénard convection.

JCPyV-Induced MAPK Signaling Activates Transcription Factors during Infection.

JC polyomavirus (JCPyV), a ubiquitous human pathogen, is the etiological agent of the fatal neurodegenerative disease progressive multifocal leukoencephalopathy (PML). Like most viruses, JCPyV infection requires the activation of host-cell signaling pathways in order to promote viral replication processes. Previous works have established the necessity of the extracellular signal-regulated kinase (ERK), the terminal core kinase of the mitogen-activated protein kinase (MAPK) cascade (MAPK-ERK) for facilitating transcription of the JCPyV genome. However, the underlying mechanisms by which the MAPK-ERK pathway becomes activated and induces viral transcription are poorly understood. Treatment of cells with siRNAs specific for Raf and MAP kinase kinase (MEK) targets proteins in the MAPK-ERK cascade, significantly reducing JCPyV infection. MEK, the dual-specificity kinase responsible for the phosphorylation of ERK, is phosphorylated at times congruent with early events in the virus infectious cycle. Moreover, a MAPK-specific signaling array revealed that transcription factors downstream of the MAPK cascade, including cMyc and SMAD4, are upregulated within infected cells. Confocal microscopy analysis demonstrated that cMyc and SMAD4 shuttle to the nucleus during infection, and nuclear localization is reduced when ERK is inhibited. These findings suggest that JCPyV induction of the MAPK-ERK pathway is mediated by Raf and MEK and leads to the activation of downstream transcription factors during infection. This study further defines the role of the MAPK cascade during JCPyV infection and the downstream signaling consequences, illuminating kinases as potential therapeutic targets for viral infection.

Optimal Noise-Canceling Networks.

Natural and artificial networks, from the cerebral cortex to large-scale power grids, face the challenge of converting noisy inputs into robust signals. The input fluctuations often exhibit complex yet statistically reproducible correlations that reflect underlying internal or environmental processes such as synaptic noise or atmospheric turbulence. This raises the practically and biophysically relevant question of whether and how noise filtering can be hard wired directly into a network's architecture. By considering generic phase oscillator arrays under cost constraints, we explore here analytically and numerically the design, efficiency, and topology of noise-canceling networks. Specifically, we find that when the input fluctuations become more correlated in space or time, optimal network architectures become sparser and more hierarchically organized, resembling the vasculature in plants or animals. More broadly, our results provide concrete guiding principles for designing more robust and efficient power grids and sensor networks.

Vortex dynamics and Lagrangian statistics in a model for active turbulence.

Cellular suspensions such as dense bacterial flows exhibit a turbulence-like phase under certain conditions. We study this phenomenon of "active turbulence" statistically by using numerical tools. Following Wensink et al. (Proc. Natl. Acad. Sci. U.S.A. 109, 14308 (2012)), we model active turbulence by means of a generalized Navier-Stokes equation. Two-point velocity statistics of active turbulence, both in the Eulerian and the Lagrangian frame, is explored. We characterize the scale-dependent features of two-point statistics in this system. Furthermore, we extend this statistical study with measurements of vortex dynamics in this system. Our observations suggest that the large-scale statistics of active turbulence is close to Gaussian with sub-Gaussian tails.

Mammography and osteoporosis screening--clinical risk factors and their association with digital X-ray radiogrammetry bone mineral density.

The aim of this study was to study the association between digital X-ray radiogrammetry (DXR) T-score and clinical risk factors for osteoporosis. Women were recruited 2 d per wk at a single mammography screening center between year 2010 and 2012. Included women answered a questionnaire about risk factors for osteoporosis, and a radiograph of the nondominant hand was obtained for DXR analysis. Univariate associations between DXR T-score and risk factors were examined. A generalized linear regression model was fitted to independent variables with univariate associations at p<0.05. The multivariable model was reduced through manual backward elimination, with p>0.1 as the exclusion criterion. Seventy-six percent of the women chose to participate in the study (n=8810). The difference in number of daily mammograms performed on study vs nonstudy days was not significant. All univariate associations between DXR T-score and potential risk factors were highly significant. The multivariable model included height, weight, age, right-handedness, menopause before age 45, alcohol consumption, cortisone treatment, rheumatic disease, and age×smoking status. The coefficient of determination of the model was 0.37. The association between risk factors for osteoporosis and DXR T-score is similar to previously reported associations with dual-energy X-ray absorptiometry.

High-throughput drug screen identifies calcium and calmodulin inhibitors that reduce JCPyV infection.

JC polyomavirus (JCPyV) is a nonenveloped, double-stranded DNA virus that infects the majority of the population. Immunocompetent individuals harbor infection in their kidneys, while severe immunosuppression can result in JCPyV spread to the brain, causing the neurodegenerative disease progressive multifocal leukoencephalopathy (PML). Due to a lack of approved therapies to treat JCPyV and PML, the disease results in rapid deterioration, and is often fatal. In order to identify potential antiviral treatments for JCPyV, a high-throughput, large-scale drug screen was performed using the National Institutes of Health Clinical Collection (NCC). Drugs from the NCC were tested for inhibitory effects on JCPyV infection, and drugs from various classes that reduced JCPyV infection were identified, including receptor agonists and antagonists, calcium signaling modulators, and enzyme inhibitors. Given the role of calcium signaling in viral infection including Merkel cell polyomavirus and simian virus 40 polyomavirus (SV40), calcium signaling inhibitors were further explored for the capacity to impact JCPyV infection. Calcium and calmodulin inhibitors trifluoperazine (TFP), W-7, tetrandrine, and nifedipine reduced JCPyV infection, and TFP specifically reduced viral internalization. Additionally, TFP and W-7 reduced infection by BK polyomavirus, SV40, and SARS-CoV-2. These results highlight specific inhibitors, some FDA-approved, for the possible treatment and prevention of JCPyV and several other viruses, and further illuminate the calcium and calmodulin pathway as a potential target for antiviral drug development.

Frailty Among Sexual and Gender Minority Older Adults: The All of Us Database.

BACKGROUND: Despite known disparities in health status among older sexual and gender minority adults (OSGM), the prevalence of frailty is unknown. The aim of this study was to develop and validate a deficit-accumulation frailty index (AoU-FI) for the All of Us database to describe and compare frailty between OSGM and non-OSGM participants. METHODS: Developed using a standardized approach, the AoU-FI consists of 33 deficits from baseline survey responses of adults aged 50+. OSGM were self-reported as "not straight" or as having discordant gender and sex assigned at birth. Descriptive statistics characterized the AoU-FI. Regression was used to assess the association between frailty, age, and gender. Validation of the AoU-FI used Cox proportional hazard models to test the association between frailty categories (robust <0.15, 0.15 ≤ pre-frail ≤ 0.25, frail >0.25) and mortality. RESULTS: There were 9 110 OSGM and 67 420 non-OSGM with sufficient data to calculate AoU-FI; 41% OSGM versus 50% non-OSGM were robust, whereas 34% versus 32% were pre-frail, and 26% versus 19% were frail. Mean AoU-FI was 0.19 (95% confidence interval [CI]: 0.187, 0.191) for OSGM and 0.168 (95% CI: 0.167, 0.169) for non-OSGM. Compared to robust, odds of mortality were higher among frail OSGM (odds ratio [OR] 6.40; 95% CI: 1.84, 22.23) and non-OSGM (OR 3.96; 95% CI: 2.96, 5.29). CONCLUSIONS: The AoU-FI identified a higher burden of frailty, increased risk of mortality, and an attenuated impact of age on frailty among OSGM compared to non-OSGM. Future work is needed to understand how frailty affects the OSGM population.

Emergence of behaviour in a self-organized living matter network.

What is the origin of behaviour? Although typically associated with a nervous system, simple organisms also show complex behaviours. Among them, the slime mold Physarum polycephalum, a giant single cell, is ideally suited to study emergence of behaviour. Here, we show how locomotion and morphological adaptation behaviour emerge from self-organized patterns of rhythmic contractions of the actomyosin lining of the tubes making up the network-shaped organism. We quantify the spatio-temporal contraction dynamics by decomposing experimentally recorded contraction patterns into spatial contraction modes. Notably, we find a continuous spectrum of modes, as opposed to a few dominant modes. Our data suggests that the continuous spectrum of modes allows for dynamic transitions between a plethora of specific behaviours with transitions marked by highly irregular contraction states. By mapping specific behaviours to states of active contractions, we provide the basis to understand behaviour's complexity as a function of biomechanical dynamics.

The statistical geometry of material loops in turbulence.

Material elements - which are lines, surfaces, or volumes behaving as passive, non-diffusive markers - provide an inherently geometric window into the intricate dynamics of chaotic flows. Their stretching and folding dynamics has immediate implications for mixing in the oceans or the atmosphere, as well as the emergence of self-sustained dynamos in astrophysical settings. Here, we uncover robust statistical properties of an ensemble of material loops in a turbulent environment. Our approach combines high-resolution direct numerical simulations of Navier-Stokes turbulence, stochastic models, and dynamical systems techniques to reveal predictable, universal features of these complex objects. We show that the loop curvature statistics become stationary through a dynamical formation process of high-curvature folds, leading to distributions with power-law tails whose exponents are determined by the large-deviations statistics of finite-time Lyapunov exponents of the flow. This prediction applies to advected material lines in a broad range of chaotic flows. To complement this dynamical picture, we confirm our theory in the analytically tractable Kraichnan model with an exact Fokker-Planck approach.

Dynamics and Patterning of 5-Hydroxytryptamine 2 Subtype Receptors in JC Polyomavirus Entry.

The organization and dynamics of plasma membrane receptors are a critical link in virus-receptor interactions, which finetune signaling efficiency and determine cellular responses during infection. Characterizing the mechanisms responsible for the active rearrangement and clustering of receptors may aid in developing novel strategies for the therapeutic treatment of viruses. Virus-receptor interactions are poorly understood at the nanoscale, yet they present an attractive target for the design of drugs and for the illumination of viral infection and pathogenesis. This study utilizes super-resolution microscopy and related techniques, which surpass traditional microscopy resolution limitations, to provide both a spatial and temporal assessment of the interactions of human JC polyomavirus (JCPyV) with 5-hydroxytrypamine 2 receptors (5-HT2Rs) subtypes during viral entry. JCPyV causes asymptomatic kidney infection in the majority of the population and can cause fatal brain disease, and progressive multifocal leukoencephalopathy (PML), in immunocompromised individuals. Using Fluorescence Photoactivation Localization Microscopy (FPALM), the colocalization of JCPyV with 5-HT2 receptor subtypes (5-HT2A, 5-HT2B, and 5-HT2C) during viral attachment and viral entry was analyzed. JCPyV was found to significantly enhance the clustering of 5-HT2 receptors during entry. Cluster analysis of infected cells reveals changes in 5-HT2 receptor cluster attributes, and radial distribution function (RDF) analyses suggest a significant increase in the aggregation of JCPyV particles colocalized with 5-HT2 receptor clusters in JCPyV-infected samples. These findings provide novel insights into receptor patterning during viral entry and highlight improved technologies for the future development of therapies for JCPyV infection as well as therapies for diseases involving 5-HT2 receptors.