Double-blind, randomized, placebo-controlled study to evaluate erenumab-specific central effects: an fMRI study.

OBJECTIVE: Given the findings of central effects of erenumab in the literature, we aimed to conduct a rigorous placebo-controlled, double-blind, randomized study to elucidate whether the observed changes are directly attributable to the drug. METHODS: We recruited 44 patients with migraine, randomly assigning them to either the erenumab 70 mg or the placebo group. 40 patients underwent fMRI scanning using a trigeminal nociceptive paradigm both, pre- and four weeks post-treatment. Participants kept a headache diary throughout the whole study period of two months in total. A clinical response was defined as a ≥30% reduction in headache frequency at follow-up. Details of this study have been preregistered in the open science framework: https://osf.io/ygf3t . RESULTS: Seven participants of the verum group (n=33.33%) and 4 of the placebo group (21.05%) experienced improvements in migraine activity, characterized by a minimum of 30% reduction in monthly headache frequency compared to baseline. The imaging data show an interaction between the verum medication and the response. Whilst numbers were too small for individual analyses (Verum vs. Placebo and Responder vs. Non-Responder), the variance-weighted analysis (Verum vs Placebo, scan before vs after weighted for response) revealed specific decrease in thalamic, opercular and putamen activity. INTERPRETATION: The central effects of erenumab could be reproduced in a placebo randomized design, further confirming its central role in migraine modulation. The mechanism, whether direct or secondary to peripheral mode of action, needs further exploration. It is important to note that the response rate to erenumab 70mg in this study was not as substantial as anticipated in 2019, when this study was planned. This resulted in a too small sample size for a subgroup analysis based on the responder status was associated with both the verum drug and the relative reduction in headache days.

Update in the understanding of new daily persistent headache.

Background Accumulating evidence suggests various specific triggers may lead to new daily persistent headache (NDPH)-like presentations, suggesting that new daily persistent headache is a heterogenous syndrome, and challenging the concept that new daily persistent headache is a primary headache disorder.Method We searched the PubMed database up to August 2022 for keywords including persistent daily headache with both primary and secondary etiologies. We summarized the literature and provided a narrative review of the clinical presentation, diagnostic work-ups, possible pathophysiology, treatment response, and clinical outcomes.Results and conclusion New daily persistent headache is a controversial but clinically important topic. New daily persistent headache is likely not a single entity but a syndrome with different etiologies. The issue with past studies of new daily persistent headache is that patients with different etiologies/subtypes were pooled together. Different studies may investigate distinct subsets of patients, which renders the inter-study comparison, both positive and negative results, difficult. The identification (and removal) of a specific trigger might provide the opportunity for clinical improvement in certain patients, even when the disease has lasted for months or years. Nonetheless, if there is a specific trigger, it remains unknown or unidentified for a great proportion of the patients. We need to continue to study this unique headache population to better understand underlying pathogenesis and, most importantly, to establish effective treatment strategies that hopefully resolve the continuous cycle of pain.

Management of cluster headache: Treatments and their mechanisms.

BACKGROUND: The management of cluster headache is similar to that of other primary headache disorders and can be broadly divided into acute and preventive treatments. Acute treatments for cluster headache are primarily delivered via rapid, non-oral routes (such as inhalation, nasal, or subcutaneous) while preventives include a variety of unrelated treatments such as corticosteroids, verapamil, and galcanezumab. Neuromodulation is becoming an increasingly popular option, both non-invasively such as vagus nerve stimulation when medical treatment is contraindicated or side effects are intolerable, and invasively such as occipital nerve stimulation when medical treatment is ineffective. Clinically, this collection of treatment types provides a range of options for the informed clinician. Scientifically, this collection provides important insights into disease mechanisms. METHODS: Two authors performed independent narrative reviews of the literature on guideline recommendations, clinical trials, real-world data, and mechanistic studies. RESULTS: Cluster headache is treated with acute treatments, bridge treatments, and preventive treatments. Common first-line treatments include subcutaneous sumatriptan and high-flow oxygen as acute treatments, corticosteroids (oral or suboccipital injections) as bridge treatments, and verapamil as a preventive treatment. Some newer acute (non-invasive vagus nerve stimulation) and preventive (galcanezumab) treatments have excellent clinical trial data for episodic cluster headache, while other newer treatments (occipital nerve stimulation) have been specifically tested in treatment-refractory chronic cluster headache. Most treatments are suspected to act on the trigeminovascular system, the autonomic system, or the hypothalamus. CONCLUSIONS: The first-line treatments have not changed in recent years, but new treatments have provided additional options for patients.

Characterization of trigeminal C-fiber reactivity through capsaicin-induced release of calcitonin gene-related peptide.

OBJECTIVE: We hypothesized that the response of trigeminal dermal blood flow (DBF) in the trigeminal system and consecutive expansion of flare response to capsaicin would differ from the somatosensory system (arm). We also investigated whether there are differences between patients with migraine and healthy controls (HC). BACKGROUND: Functional differences between the trigeminal and extracephalic somatosensory systems may partly explain the susceptibility for headaches in patients with migraine. Capsaicin-induced activation of nociceptive C-fibers in the skin is mainly mediated by calcitonin gene-related peptide (CGRP) and induces cutaneous vessel dilatation and flare response. METHODS: Female patients with migraine (n = 38) and age-matched HC (n = 35) underwent DBF measurement at baseline and after topical capsaicin administration using laser speckle imaging. DBF before and after capsaicin stimulation was analyzed over ophthalmic nerve/maxillary nerve/mandibular nerve (V1/V2/V3) dermatomes and the forearm as an extracephalic control. RESULTS: Capsaicin-induced DBF increased more in the trigeminal dermatomes than on the forearm. The V1 dermatome showed a smaller increase of DBF in patients with migraine compared to HC. CONCLUSION: Our results suggest that the trigeminovascular system reacts differently from extracephalic areas, which may explain the trigeminal susceptibility to CGRP-mediated pain attacks. By demonstrating a different reactivity of the V1 dermatome in patients with migraine, our finding suggests that the first trigeminal branch is functionally different from the second and third branches; however, only in patients with migraine.

Carditis After COVID-19 Vaccination With a Messenger RNA Vaccine and an Inactivated Virus Vaccine : A Case-Control Study.

BACKGROUND: Case reports of carditis after BNT162b2 vaccination are accruing worldwide. OBJECTIVE: To examine the association of BNT162b2 and CoronaVac (Sinovac) vaccination with carditis. DESIGN: Case-control study with hospital control participants. SETTING: Territory-wide, public health care database with linkage to population-based vaccination records in Hong Kong. PATIENTS: Inpatients aged 12 years or older first diagnosed with carditis were selected as case patients. All other hospitalized patients without carditis were treated as control participants. Ten control participants were randomly matched with each case patient by age, sex, and admission date. INTERVENTION: Vaccination with BNT162b2 or CoronaVac. MEASUREMENTS: Incident diagnosis of carditis based on the International Classification of Diseases, Ninth Revision, and elevated troponin levels. RESULTS: A total of 160 case patients and 1533 control participants were included. Incidence of carditis per 100 000 doses of CoronaVac and BNT162b2 administered was estimated to be 0.31 (95% CI, 0.13 to 0.66) and 0.57 (CI, 0.36 to 0.90), respectively. Multivariable analyses showed that recipients of the BNT162b2 vaccine had higher odds of carditis (adjusted odds ratio [OR], 3.57 [CI, 1.93 to 6.60]) than unvaccinated persons. Stratified by sex, the OR was 4.68 (CI, 2.25 to 9.71) for males and 2.22 (CI, 0.57 to 8.69) for females receiving the BNT162b2 vaccine. The ORs for adults and adolescents receiving the BNT162b2 vaccine were 2.41 (CI, 1.18 to 4.90) and 13.79 (CI, 2.86 to 110.38), respectively. Subanalysis showed an OR of 9.29 (CI, 3.94 to 21.91) for myocarditis and 1.06 (CI, 0.35 to 3.22) for pericarditis associated with BNT162b2. The risk was mainly seen after the second dose of BNT162b2 rather than the first. No association between CoronaVac and carditis with a magnitude similar to that for BNT162b2 was seen. LIMITATION: Limited sample size, absence of electrocardiography and other clinical investigative data, and unrecorded overseas vaccination exposure. CONCLUSION: Despite a low absolute risk, there is an increased risk for carditis associated with BNT162b2 vaccination. This elevated risk should be weighed against the benefits of vaccination. PRIMARY FUNDING SOURCE: Health and Medical Research Fund.

Cycling multisensory changes in migraine: more than a headache.

PURPOSE OF REVIEW: Research on migraine usually focuses on the headache; however, accumulating evidence suggests that migraine not only changes the somatosensory system for nociception (pain), but also the other modalities of perception, such as visual, auditory or tactile sense. More importantly, the multisensory changes exist beyond the headache (ictal) phase of migraine and show cyclic changes, suggesting a central generator driving the multiple sensory changes across different migraine phases. This review summarizes the latest studies that explored the cyclic sensory changes of migraine. RECENT FINDINGS: Considerable evidence from recent neurophysiological and functional imaging studies suggests that alterations in brain activation start at least 48 h before the migraine headache and outlast the pain itself for 24 h. Several sensory modalities are involved with cyclic changes in sensitivity that peak during the ictal phase. SUMMARY: In many ways, migraine represents more than just vascular-mediated headaches. Migraine alters the propagation of sensory information long before the headache attack starts.

Post-Covid-19-vaccination adverse events and healthcare utilization among individuals with or without previous SARS-CoV-2 infection.

BACKGROUND: Post-marketing pharmacovigilance data are scant on the safety of Covid-19 vaccines among people with previous SARS-CoV-2 infection compared with ordinary vaccine recipients. We compared the post-vaccination adverse events of special interests (AESI), accident and emergency room (A&E) visit, and hospitalization between these two groups. METHODS: We conducted a retrospective cohort study using a territory-wide public healthcare database with population-based vaccination records in Hong Kong. RESULTS: In total, 3922 vaccine recipients with previous SARS-CoV-2 infection and 1,137,583 vaccine recipients without previous SARS-CoV-2 infection were included. No significant association was observed between previous SARS-CoV-2 infection and AESI or hospitalization. Previous SARS-CoV-2 infection was significantly associated with a lower risk of A&E visit (CoronaVac: hazard ratios [HR] = 0.56, 95% confidence intervals [CI]: 0.32-0.99; Comirnaty: HR = 0.62, 95% CI: 0.47-0.82). CONCLUSION: No safety signal of Covid-19 vaccination was detected from the comparison between vaccine recipients with previous SARS-CoV-2 infection and those without infection.

Multiplexed LC-MS/MS analysis of methylsuccinic acid, ethylmalonic acid, and glutaric acid in plasma and urine.

Low molecular-mass aliphatic carboxylic acids are critically important for intermediate metabolism and may serve as important biomarkers for metabolic homeostasis. Here in, we focused on multiplexed method development of aliphatic carboxylic analytes, including methylsuccinic acid (MSA), ethylmalonic acid (EMA), and glutaric acid (GA). Also assessed was their utility in a population's health as well as metabolic disease screening in both plasma and urine matrices. MSA, EMA, and GA are constitutional isomers of dicarboxylic acid with high polarity and poor ionization efficiency, resulting in such challenges as poor signal intensity and retention, particularly in reversed-phase liquid chromatography with electrospray mass spectrometry (RP-LC-ESI-MS/MS). Derivatization using n-butanol was performed in the sample preparation to enhance the signal intensity accompanied with a positive charge from ionization in complicated biomatrices as well as to improve the separation of these isomers with optimal retention. Fit-for-purpose method validation results demonstrated quantitative ranges for MSA/EMA/GA from 5/10/20 ng/mL to 400 ng/mL in plasma analysis, and 100/200/100 ng/mL to 5000/10000/5000 ng/mL in urine analysis. This validated method demonstrates future utility when exploring population health analysis and biomarker development in metabolic diseases.

Aura in trigeminal autonomic cephalalgia is probably mediated by comorbid migraine with aura.

OBJECTIVE: The presence of aura is rare in cluster headache, and even rarer in other trigeminal autonomic cephalalgias. We hypothesized that the presence of aura in patients with trigeminal autonomic cephalalgias is frequently an epiphenomenon and mediated by comorbid migraine with aura. METHODS: The study retrospectively reviewed 480 patients with trigeminal autonomic cephalalgia in a tertiary medical center for 10 years. Phenotypes and temporal correlation of aura with headache were analyzed. Trigeminal autonomic cephalalgia patients with aura were further followed up in a structured telephone interview. RESULTS: Seventeen patients with aura (3.5%) were identified from 480 patients with trigeminal autonomic cephalalgia, including nine with cluster headache, one with paroxysmal hemicrania, three with hemicrania continua, and four with probable trigeminal autonomic cephalalgia. Compared to trigeminal autonomic cephalalgia patients without aura, trigeminal autonomic cephalalgia patients with aura were more likely to have a concomitant diagnosis of migraine with aura (odds ratio [OR] = 109.0, 95% CI 30.9-383.0, p < 0.001); whereas the risk of migraine without aura remains similar between both groups (OR = 1.10, 95% CI = 0.14-8.59, p = 0.931). Aura was more frequently accompanied with migraine-like attacks, but not trigeminal autonomic cephalalgia attacks. INTERPRETATION: In most patients with trigeminal autonomic cephalalgia, the presence of aura is mediated by the comorbidity of migraine with aura. Aura directly related to trigeminal autonomic cephalalgia attack may exist but remains rare. Our results suggest that aura may not be involved in the pathophysiology of trigeminal autonomic cephalalgia.

Galcanezumab modulates Capsaicin-induced C-fiber reactivity.

BACKGROUND: The vasodilatory calcitonin-gene related peptide (CGRP) is understood as pivotal mediator in migraine pathophysiology. Blocking CGRP with small molecules or monoclonal antibodies (CGRP-mAb) reduces migraine frequency. However, prescription of CGRP-mAbs is still regulated and possible predictive measures of therapeutic success would be useful. METHODS: Using standardized capsaicin-induced dermal blood flow model, 29 migraine patients underwent a laser speckle imaging measurement before and after administration of galcanezumab. At both sessions dermal blood flow before and after capsaicin stimulation as well as flare size were analyzed over all three trigeminal branches and the volar forearm for extracranial control. Long-term measures were repeated in 14 patients after continuous treatment ranging from 6 to 12 months. RESULTS: Resting dermal blood flow remained unchanged after administration of galcanezumab. Capsaicin-induced dermal blood flow decreased significantly after CGRP-mAb in all tested areas compared to baseline and this was consistent even after 12 months of treatment. However, following galcanezumab administration, the flare size decreased only in the three trigeminal dermatomes, not the arm and was therefore specific for the trigemino-vascular system. None of these two markers distinguished between responders and non-responders. CONCLUSION: CGRP-mAb changed blood flow response to capsaicin stimulation profoundly and this effect did not change over a 12-month application. Neither capsaicin-induced flare nor dermal blood flow can be used as a predictor for treatment efficacy. These data suggest that the mechanism of headache development in migraine is not entirely CGRP-mediated.

Update of New Daily Persistent Headache.

PURPOSE OF REVIEW: The diagnostic criteria of new daily persistent headache (NDPH) have been revised since 2013. The current review focused on the progress of NDPH research over the last few years. RECENT FINDINGS: Various new triggers and different NDPH mimics have been reported. The association with both cephalic and extracephalic pathologies suggests that NDPH is rather a syndrome with more than one disease mechanism. Recent clinical studies confirmed that migrainous headache remained the most prominent phenotype of NDPH, echoing the change of the diagnostic criteria in 2013. Diagnostic workup, including imaging studies, was unremarkable, except serving to exclude secondary etiologies. Studies on treatment options have yet shown promising targets, and randomized clinical trials are still lacking. Multiple mechanisms, both cranial and systemic, may be involved synergically in the generation of NDPH-like headaches. The search for effective treatment options should base on better understanding of disease mechanisms.

Effect of g-C3N4 on biodiversity and structure of bacterial community in sediment of Xiangjiang River under tetracycline pressure.

Photocatalysts have been widely prepared and used in wastewater treatment. Although the influence of photocatalyst application on survival and activity of organisms has been examined, its impact on composition and diversity of microbial community is not fully understood. In this study, the impact of photocatalyst g-C3N4 (Graphitic carbon nitride) on microbial communities in riverbed sediments polluted by antibiotic tetracycline (TC) was investigated. The sediment samples collected from the Xiangjiang River of China were exposed to different concentrations of TC, g-C3N4 and TC/g-C3N4 and the bacterial community were analyzed by Illumina sequencing. The results showed that the dominant bacterial phyla were Acidobacteriota, Proteobacteria, Actinobacteriota, and Chloroflexi in the study site. When compared to the control treatments, the application of TC, g-C3N4 and TC/g-C3N4 exhibited distinguishable effects on bacterial community structure in sediments. The presence of TC had greater influence on bacterial composition, while g-C3N4 and TC/g-C3N4 had less influence on bacteria. The diversity and richness of microorganisms in sediment increased under g-C3N4 application and reached the highest values when g-C3N4 was 75 mg/kg. The photocatalyst g-C3N4 restored bacterial community diversity affected by TC, reduced the TC residues in aquatic environment, and eliminated the side effects of TC application in sediments. Our study indicated that g-C3N4 was an environmentally friendly photocatalyst with lightly negative effects on microbial community in riverbed sediments, and could be used for effective remediation of TC-contaminated environments.

Debate: Are cluster headache and migraine distinct headache disorders?

Cluster headache and migraine are regarded as distinct primary headaches. While cluster headache and migraine differ in multiple aspects such as gender-related and headache specific features (e.g., attack duration and frequency), both show clinical similarities in trigger factors (e.g., alcohol) and treatment response (e.g., triptans). Here, we review the similarities and differences in anatomy and pathophysiology that underlie cluster headache and migraine, discuss whether cluster headache and migraine should indeed be considered as two distinct primary headaches, and propose recommendations for future studies. Video recording of the debate held at the 1st International Conference on Advances in Migraine Sciences (ICAMS 2022, Copenhagen, Denmark) is available at https://www.youtube.com/watch?v=uUimmnDVTTE .

Redefining migraine phases - a suggestion based on clinical, physiological, and functional imaging evidence.

Migraine is defined by attacks of headache with a specific length and associated symptoms such as photophobia, phonophobia and nausea. It is long recognized that migraine is more than just the attacks and that migraine should be understood as a cycling brain disorder with at least 4 phases: interictal, preictal, ictal and postictal. However, unlike the pain phase, the other phases are less well defined, which renders studies focusing on these phases susceptible to bias. We herewith review the available clinical, electrophysiological, and neuroimaging data and propose that the preictal phase should be defined as up to 48 hours before the headache attack and the postictal phase as up to 24 hours following the ictal phase. This would allow future studies to specifically investigate these migraine phases and to make study results more comparable.

Cluster headache in Asian populations: Similarities, disparities, and a narrative review of the mechanisms of the chronic subtype.

OBJECTIVE: Headache disorders like migraine show geographic and ethnic differences between Asian and European/North American countries. In cluster headache, these differences are rarely mentioned and discussed. This article aimed to review the characteristics of cluster headache in Asian countries and compare the clinical features to those in European and North American populations. METHODS: We conducted a narrative literature review on the demographics, clinical presentations, and treatments of cluster headache in Asian countries. RESULTS: Patients with cluster headache in Asian populations showed a stronger male predominance compared to European and North American populations. Chronic cluster headache was rare in Asian countries. The clinical presentation of restlessness was not as common in Asian as it was in European and North American countries, and Asian patients with aura were extremely rare. Patients in Asian countries may have a lower circadian rhythmicity of cluster headache and a lower headache load, as demonstrated by lower attack frequencies per day, bout frequencies, and bout durations. CONCLUSIONS: Regional differences in the presentation of cluster headache exist. Greater awareness for cluster headache should be raised in Asian regions, and further studies are warranted to elucidate the mechanisms behind observed differences.

Three-dimensional synthetic aperture focusing photoacoustic microscopy based on the acoustic simulation generated delay time and weighted factor.

Acoustic resolution photoacoustic microscopy (ARPAM) is a promising imaging tool in biomedical applications for its advantage of penetration over other optical imaging techniques. However, the lateral resolution of ARPAM deteriorates significantly in the out-of-focus region. The synthetic aperture focusing technique (SAFT) is required to restore this kind of focus-related imaging distortion. The conventional SAFT method is based on the virtual detector (VD) conception, in which the phase of the received photoacoustic (PA) signal is calculated by assuming the focus of the transducer as a VD. Nevertheless, the phase of the received PA signal is not only determined by the geometrical parameters of the transducer, but also by the transducer's electromechanic response and the original PA signal. Ignoring these two factors will reduce the quality of the imaging results. In this work, a new SAFT method, which is based on acoustic simulation, is proposed for ARPAM. The measured PA signal from a point target at the focus is employed to evaluate the convolution of the transducer's electromechanic response and the original PA signal. This measured signal is used as the excitation in an acoustic simulation. The simulation, which is based on the geometrical and acoustic parameters of the transducer, is employed to calculate the delay time and weighted coefficient for the SAFT calculation. The phantom experiments with point and line targets indicate that the proposed method obtains imaging results with better lateral resolution and improved signal-noise ratio compared with the widely used VD-based SAFT method.

Current understanding of premonitory networks in migraine: A window to attack generation.

AIM: To describe neuronal networks underlying commonly reported migraine premonitory symptoms and to discuss how these might precipitate migraine pain. BACKGROUND: Migraine headache is frequently preceded by a distinct and well characterized premonitory phase including symptoms like yawning, sleep disturbances, alterations in appetite and food intake and hypersensitivity to certain external stimuli. Recent neuroimaging studies strongly suggest the hypothalamus as the key mediator of the premonitory phase and also suggested alterations in hypothalamic networks as a mechanism of migraine attack generation. When looking at the vast evidence from basic research within the last decades, hypothalamic and thalamic networks are most likely to integrate peripheral influences with central mechanisms, facilitating the precipitation of migraine headaches. These networks include sleep, feeding and stress modulating centers within the hypothalamus, thalamic pathways and brainstem centers closely involved in trigeminal pain processing such as the spinal trigeminal nucleus and the rostral ventromedial medulla, all of which are closely interconnected. CONCLUSION: Taken together, these networks represent the pathophysiological basis for migraine premonitory symptoms as well as a possible integration site of peripheral so-called "triggers" with central attack facilitating processes.

Risk factors and psychological impact of syncope in migraine patients.

BACKGROUND: Migraine is associated with syncope. We investigated risk factors for syncope and burden of syncope in migraine patients. METHODS: Participants were recruited from a headache clinic. All participants provided information on lifestyle, co-morbidity, syncope, headache and suicide, and completed the MIDAS and HADS questionnaires. Genetic data were available for a subset of participants. Risk of syncope in relation to participant's characteristics and migraine susceptibility loci, and risks of psychological disorders associated with syncope, were calculated using logistic regression. RESULTS: Underweight, regular tea intake, diabetes mellitus, and migraine with aura were associated with increased syncope risks, with adjusted ORs of 1.76 (95% CI 1.03-3.03), 1.84 (95% CI 1.22-2.79), 4.70 (95% CI 1.58-13.95), and 1.78 (95% CI 1.03-3.10), respectively. Preliminary results showed that rs11172113 in LRP1 was associated with syncope risks. Comorbid syncope in migraine patients was associated with increased risks of depression (OR 1.95, 95% CI 1.18-3.22) and suicide attempt (OR 2.85, 95% CI 1.48-5.48). CONCLUSION: Our study showed the potential roles of vascular risk factors in the association between migraine and syncope. Modifiable risk factors for syncope in patients with migraine include body mass index and tea intake. The debilitating psychological impact of co-morbid syncope in migraine patients warrants clinical attention of treating physicians.

TIM-1 As a Signal Receptor Triggers Dengue Virus-Induced Autophagy.

Dengue virus (DENV) infection triggers the activation of autophagy to facilitate the viral replication cycle from various aspects. Although a number of stimulators are proposed to activate autophagy, none of them appears prior to the uncoating process. Given that T-cell immunoglobulin and mucin domain 1 (TIM-1) receptor is a putative DENV receptor and promotes apoptotic body clearance by autophagy induction, it raises the possibility that TIM-1 may participate in the activation of DENV-induced autophagy. In this study, confocal images first revealed the co-localization of TIM-1 with autophagosomes in DENV-induced autophagy rather than rapamycin-induced autophagy, suggesting the co-transportation of TIM-1 with DENV during infection. The treatment of siRNA to knockdown TIM-1 expression in DENV-infected GFP-microtubule-associated protein light chain 3 (LC3)-Huh7.5 cells revealed that TIM-1 is required not only for DENV cellular internalization but also for autophagy activation. Furthermore, knockdown p85, a subunit of phosphoinositide 3-kinases (PI3Ks), which is co-localized with TIM-1 at rab5-positive endosomes caused the reduction of autophagy, indicating that TIM-1-mediated DENV-induced autophagy requires p85. Taken together, the current study uncovered TIM-1 as a novel factor for triggering autophagy in DENV infection through TIM-1-p85 axis, in addition to serving as a DENV receptor.