Herpes Simplex Virus Infection Research Articles

Association of herpes simplex virus infection and vitiligo: a nationwide retrospective cohort study.

Several studies have proposed viral infection with herpes simplex virus (HSV) as a probable cause of vitiligo. We aimed to examine the association between HSV infection and vitiligo. We used the National Health Insurance Research Database of Taiwan to perform a comparative analysis of the study population with or without a diagnosis of HSV infection. The study period was from January 1st, 2008, to December 31st, 2019. The primary outcome was the date of first vitiligo diagnosis, death, withdrawal from the National Health Insurance Program, or end of the study. We performed 1:1 propensity score matching based on age, sex, and comorbidities, resulting in 1,009,445 matched pairs of patients with and without HSV infections. The adjusted hazard ratio for developing vitiligo in the HSV cohort was 1.71 (95% confidence interval, 1.59 - 1.83; P < 0.001). An age-dependent pattern was also observed among HSV-infected patients with vitiligo (P for interaction < 0.001). Both sexes exhibited a significantly higher risk of developing vitiligo in the presence of HSV infection. The HSV cohort significantly increased cumulative vitiligo risk compared to the non-HSV cohort in a 12-year follow-up (log-rank P < 0.001). The result of sensitivity analysis was compatible with that of primary analysis. Patients with HSV infection had a considerably increased vitiligo risk within the 1-year follow-up than the non-HSV cohort (adjusted hazard ratio, 4.83; 95% confidence interval, 4.04 - 5.77, P < 0.001). This nationwide population-based study demonstrated an association between HSV infection and an increased risk of vitiligo. Further investigation of HSV DNA in the affected regions of vitiligo lesions may help to establish causality.

Nanocrystals in Dermal Drug Delivery: A Breakthrough for Enhanced Skin Penetration and Targeted Skin Disorder Treatments

One of the major challenges in dermal drug delivery is the adequate penetration of the active compound into the skin without causing any skin irritation and inflammation. Nanocrystals (NCs) are nanoscale particles, and their sizes are below 1000 nm. NCs are made up of drug particles only, which are used to improve the aqueous solubility and bioavailability of poorly water-soluble drugs. NCs are typically prepared either by bottom-up or top-down techniques. The advantages of using NC-based formulations in enhancing dermal drug delivery include increased drug loading capacity, easier and deeper penetration into the skin tissue, and increased passive diffusion. NC-based formulations with the capacity of enhanced dermal drug delivery can be effectively used to treat a wide range of skin disorders, including melanoma, inflammation, psoriasis, acne vulgaris, bacterial infections, fungal infections, eczema, skin aging, herpes simplex virus infections, skin manifestations of tick bites, frostbite-related infections, hyperpigmentation, and diabetic foot ulcer. In this review, major challenges in dermal drug delivery across the skin barrier, mechanism of action of dermal NCs, advantages of using NCs in enhancing dermal drug delivery, NC preparation methods, and applications of NCs in the treatment of various skin disorders have been discussed.

A Complex Case of Acute Liver Failure Following Idiosyncratic Drug-Induced Liver Injury, Potentiated by Herpes Simplex Virus Infection

A Complex Case of Acute Liver Failure Following Idiosyncratic Drug-Induced Liver Injury, Potentiated by Herpes Simplex Virus Infection

Next-generation 3D printed multipurpose prevention intravaginal ring for prevention of HIV, HSV-2, and unintended pregnancy

Globally, nearly half of all pregnancies are unintended, ∼1.3 million new human immunodeficiency virus (HIV) infections are reported every year, and more than 500 million people are estimated to have a genital herpes simplex virus (HSV-2) infection. Here we report the first 3D printed multipurpose prevention technology (MPT) intravaginal ring (IVR) for prevention of HIV, HSV-2, and unintended pregnancy. The IVRs were fabricated using state-of-the-art Continuous Liquid Interface Production (CLIP™) 3D printing technology using a biocompatible silicone-urethane based resin. Anti-HIV drug (Dapivirine, DPV), anti-herpes drug (Pritelivir, PTV) and a contraceptive drug (Levonorgestrel, LNG) were loaded in a macaque size IVR (25 mm outer diameter, OD; 6.0 mm cross-section, CS) allometrically scaled from the human size (54 mm OD; 7.6 mm CS) IVR analogue. All three active pharmaceutical ingredients (APIs) were loaded in the IVR using a single-step drug loading process driven by absorption. DPV, PTV, and LNG elicited zero-order release kinetics in vitro in simulated vaginal fluid (SVF) at pH 4 and pH 8 relevant to human and macaque vaginal pH respectively. CLIP 3D printed MPT IVRs remained stable after 6 months of storage at 4 °C with no change in physical, dimensional, or mechanical properties and no change in drug concentration and absence of drug degradation byproducts. The MPT IVRs elicited sustained release of all three APIs in macaques for 28 days with median plasma concentrations of 138 pg/mL (DPV), 18,700 pg/mL (PTV), and 335 pg/mL (LNG). Safety studies demonstrated that the MPT IVRs were safe and well tolerated in the macaques with no observed change or abnormalities in vaginal pH and no significant changes in any of the 22 mucosal cytokines and chemokines tested including pro-inflammatory (IL-1β, IL-6, IL-8, IFN-γ, TNF-α, IL-17, IL-18) and anti-inflammatory (IL-10, IL-12) cytokines while the MPT IVR was in place or after its removal. Additionally, MPT IVRs elicited no observed alterations in systemic CD4+ and CD8+ T cells during the entire study. Collectively, the proposed MPT IVR has potential to expand preventative choices for young women and girls against unintended pregnancy and two highly prevalent sexually transmitted infections (STIs).

Herpes simplex virus-1 targets the 2′-3'cGAMP importer SLC19A1 as an antiviral countermeasure

The extracellular addition of the STING agonist, 2-3cGAMP, induces an antiviral state that inhibits HSV-1 replication in a cell type dependent manner via the transportation of the cyclic-dinucleotide through the folate antiporter SLC19A1. To establish a successful infection, herpes simplex virus-1 (HSV-1), a ubiquitous virus with high seropositivity in the human population, must undermine a multitude of host innate and intrinsic immune defense mechanisms, including key players of the STimulator of INterferon Genes (STING) pathway. Herein, we report that HSV-1 infection results in the reduction of SLC19A1 transcription, translation, and importantly, the rapid removal of SLC19A1 from the cell surface of infected cells. Our data indicate SLC19A1 functions as a newly identified antiviral mediator for extracellular 2′-3'cGAMP which is undermined by HSV-1 protein ICP27. This work presents novel and important findings about how HSV-1 manipulates the host's immune environment for viral replication and discovers details about an important antiviral mechanism.

Sulfated Cellulose Nanofiber Hydrogel with Mucus-Like Activities for Virus Inhibition.

Mucus is the first defense barrier against viruses in the human immune system. Inspired by the mucus structure, we designed a highly sulfated hydrogel to bind viruses and prevent infection of the underlying cells. The hydrogel was formed by gelation of sulfated cellulose nanofiber (SCNF) with Ca2+. SCNF exhibited a mucin-like nanofiber structure with high numbers of sulfated groups. Based on the electrostatic interactions with a virus, SCNF could efficiently inhibit herpes simplex virus-1 (HSV-1) infection with a half-maximal inhibitory concentration (IC50) of 0.43 μg/mL, which is comparable to that of heparin (IC50 = 0.30 μg/mL). Benefiting from the multiporous structure and sulfate groups, the Ca2+-SCNF hydrogel could efficiently trap HSV-1 and inhibit the virus from attacking the underlying cells in a transwell model. Furthermore, SCNF also inhibited SARS-CoV-2 infection in a similar experimental setting. By integrating the advantages of high and broad-spectrum virus inhibitory activity as well as low toxicity, it is believed that the Ca2+-SCNF hydrogel can promote the development of highly biocompatible and efficient antiviral material with "binding and inhibition" capability and other diverse strategies.

Herpes stromal keratitis erodes the establishment of tissue-resident memory T cell pool in HSV-1 infected corneas

The recurrent herpes simplex virus-1 (HSV-1) infection of the cornea can cause the development of herpes stromal keratitis (HSK). This chronic immunoinflammatory condition is a major cause of infection-induced vision loss. The previous episodes of HSK increase the risk of future recurrences in the same cornea. However, not all HSV-1 infected corneas that shed infectious virus at the ocular surface develop HSK, suggesting that corneal HSV-1 infection may cause an establishment of protective immunity in HSV-1 infected corneas. However, upon recurrent corneal HSV-1 infection, the established protective immunity can get compromised, resulting in the development of HSK. In this study, we compared the quantity and quality of tissue-resident memory T (TRM) cells in HSV-1 infected corneas that did or did not develop HSK. Our results showed the predominance of TRM cell in the epithelium than in stroma of HSV-1 infected corneas. Furthermore, HSV-1 infected non-HSK corneas exhibited more CD4 and CD8 TRM cells than HSK corneas. The TRM cells in non-HSK than in HSK corneas were more effective in clearing the infectious virus upon secondary corneal HSV-1 infection. Our results demonstrate the differential quantity and quality of TRM cells in HSV-1 infected corneas that did or did not develop HSK.

Improving antibody-mediated protection against HSV infection by eliminating interactions with the viral Fc receptor gE/gI.

Herpes simplex virus (HSV) encodes surface glycoproteins that are host defense evasion molecules, allowing the virus to escape immune clearance. In addition to their role in neuropathogenesis and cell-cell spread, glycoproteins E and I (gE/gI) form a viral Fc receptor (vFcR) for most subclasses and allotypes of human IgG and promote evasion of humoral immune responses. While monoclonal antibodies (mAbs) protect mice from neonatal HSV (nHSV) infections, the impact of the vFcR on mAb-mediated protection by binding to IgG is unknown. Using HSV-1 with intact and ablated gE-mediated IgG Fc binding, and Fc-engineered antibodies with modified ability to interact with gE/gI, we investigated the role of the vFcR in viral pathogenesis and mAb-mediated protection from nHSV. The gD-specific human mAb HSV8 modified to lack binding to gE exhibited enhanced neutralization and in vivo protection compared to its native IgG1 form. This improved protection by the engineered mAbs was dependent on the presence of the vFcR. Human IgG3 allotypes lacking vFcR binding also exhibited enhanced antiviral activity in vivo, suggesting that vaccines that robustly induce IgG3 responses could show enhanced protection. suggesting the value of vaccination strategies that robustly induce this subclass. Lastly, analysis of longitudinal responses to acute primary genital infection in humans raised the possibility that unlike most viruses, HSV may exhibited slow induction of IgG3. In summary, this study demonstrates that mAbs lacking the ability to interact with the vFcR can exhibit improved protection from HSV-offering new prospects for antibody-based interventions.

Breaching the Barrier: Investigating Initial Herpes Simplex Viral Infection and Spread in Human Skin and Mucosa.

Herpes simplex virus (HSV) is sexually transmitted via the anogenital mucosa where it initially infects epidermal keratinocytes and mononuclear phagocytes (MNPs). It then spreads to the dorsal root ganglion via sensory nerve endings, to remain latent for life with periodic reactivation. Currently, there is no cure or vaccine. Initial or recurrent HSV infection can produce serious complications and mediate acquisition of HIV. This review outlines the initial events after the HSV infection of human anogenital mucosa to determine the optimal window to target the virus before it becomes latent. After infection, HSV spreads rapidly within the mid-layers of epidermal keratinocytes in the explanted human inner foreskin. Infected cells produce chemokines, which modulate nectin-1 distribution on the surface of adjacent keratinocytes, facilitating viral spread. Epidermal Langerhans cells and dendritic cells become infected with HSV followed by a "viral relay" to dermal MNPs, which then present viral antigen to T cells in the dermis or lymph nodes. These data indicate the need for interruption of spread within 24 h by diffusible vaccine-induced mediators such as antiviral cytokines from resident immune cells or antibodies. Intradermal/mucosal vaccines would need to target the relevant dermal MNPs to induce HSV-specific CD4+ and CD8+ T cells.

Parenteral aciclovir for suspected herpes simplex virus infection in children: 0–18 years

Abstract Background Variations in neonatal aciclovir prescribing for suspected herpes simplex virus (HSV) disease are well-known, but there are limited data describing aciclovir prescribing in older children. Methods Medical records of neonates (≤28 days) and children (29 days to 18 years) prescribed intravenous aciclovir for suspected HSV disease (1 January 2019–12 December 2019) in eight Australian and New Zealand hospitals were reviewed. Prescribing indication, HSV testing, aciclovir prescription details, adverse events and discharge diagnosis were recorded. Results 1426 received empirical aciclovir. For neonates (n = 425), the median duration was 1 day (IQR 1–3), 411/425 underwent HSV investigations and 13/425 had HSV disease (two with disseminated encephalitis, four with encephalitis and seven with skin, eye, mouth disease). Of the 1001 children, 906 were immunocompetent. 136/906 suspected of mucocutaneous disease received aciclovir for a median of 2 days (1–2), 121/136 underwent HSV testing, and 69/136 had proven disease. 770/906 received aciclovir for suspected disseminated disease or encephalitis for a median of 1 day (1–2), 556/770 underwent HSV testing, and 5/770 had disseminated disease or encephalitis. Among 95 immunocompromised children, 53/58 with suspected mucocutaneous disease had HSV testing and this was confirmed in 22. Disseminated disease or encephalitis was suspected in 37/95, HSV testing conducted in 23/37 and detected in one. The median aciclovir duration was 3 (2–7) days for immunocompromised children. Nephrotoxicity occurred in 7/1426 and 24/1426 had an extravasation injury. Conclusion Frequent and often unnecessary intravenous aciclovir prescribing for suspected HSV encephalitis or disseminated disease occurred in children, as evidenced by incomplete HSV investigations and only 5/770 older children having the diagnosis confirmed.

The herpes simplex virus alkaline nuclease is required to maintain replication fork progression.

Herpes simplex virus 1 (HSV-1) is a near-ubiquitous pathogen within the global population, causing a lifelong latent infection with sporadic reactivation throughout the life of the host. Within at-risk and immunocompromised communities, HSV-1 infection can cause serious morbidities including herpes keratitis and encephalitis. With the possibility of herpesviruses to evade established antiviral therapies and there being no approved HSV-1 vaccine, there comes a need to investigate potential targets for intervention against infection and subsequent disease. UL12 is the viral 5'-3' exonuclease, which is required for the production of infectious progeny. In this study, we show that in the absence of UL12, viral replication fork progression is abrogated. These data point to UL12 as an attractive target for intervention, which could lead to better clinical outcomes of HSV-1-associated disease in the future.

Disseminated herpes simplex virus infection in pregnancy

Herpes simplex virus (HSV) types 1 and 2 produce the most common sexually transmitted infection in women, with a higher incidence reported in developing countries. When the first infection occurs during the perinatal period, it can spread, resulting in high morbidity and mortality of the mother and child, in addition to mainly neurological sequelae in the newborn. Despite having reliable laboratory tests, the diagnosis of herpes simplex virus infection in this population is complex since the clinical presentation ranges from asymptomatic or with non-specific symptoms without lesions on the skin or mucous membranes. For this reason, a high clinical suspicion is necessary. Here, we present the case of a mother with disseminated herpes simplex virus type 2 infection with viral hepatitis and fetal death, highlighting the importance of suspecting the diagnosis in febrile women with systemic compromise during the perinatal period, even in the absence of rash.

γδ T17 Cells Regulate the Acute Antiviral Response of NK Cells in HSV-1-Infected Corneas.

To determine whether γδ T cells regulate natural killer (NK) cells in the herpes simplex virus 1 (HSV-1)-infected cornea. CD57Bl/6 (wild-type [WT]), TCRδ-/-, and IFN-γ-/- mice were infected intracorneally with HSV-1. TCR-/- mice were treated with IL-17A at 24 hours post-infection (PI), and the WT mice received treatments of fingolimod (FTY720) and anti-IL-17A. At 48hours PI, corneas were excised, and intracellular staining flow cytometry was performed, as well as multiplex analysis. Additionally, single-cell RNA sequencing (scRNAseq) was done to analyze the transcriptome of NK cells from WT and TCRδ-/- mice. In mice lacking γδ T cells, there were significantly fewer NK cells following ocular HSV-1 infection. This reduction of NK cells corresponded with lower levels of cytokines and chemokines associated with the antiviral response. Furthermore, NK cells from WT mice had enriched IL-17A signaling compared to those from TCRδ-/- mice. The NK cell response was partially rescued in TCRδ-/- mice by administration of IL-17A. Correspondingly, the NK cell response could be blunted in WT mice by administration of anti-IL-17A. Finally, IFN-γ-/- mice had significantly less IL-17A production compared to WT mice. γδ T17 cells promote NK cell accumulation in HSV-1-infected corneas. In turn, NK cells secrete IFN-γ, which negatively regulates further IL-17A production by γδ T cells.

CRISPR-Cas12a based HSV DNA detection method using quantum dot-labeled immunochromatographic strips

Herpes simplex virus (HSV) infection poses a significant public health challenge, particularly affecting vulnerable populations such as pregnant women, newborns, and immunocompromised individuals. Traditional diagnostic methods for HSV are often time-consuming, requiring specialized expertise and infrastructure, resulting in delays and limitations in resource-limited regions. In this research, we established a novel detection method that integrates CRISPR-Cas12a with Recombinase Assisted Amplification (RAA), enabling the sensitive and specific detection of HSV DNA. Compared to TaqMan PCR, our CRISPR-Cas12a-based lateral flow assay (CRI-LFA) using universal primers demonstrated a sensitivity of 90.38 %, specificity of 98.08 %, positive predictive value (PPV) of 100 %, negative predictive value (NPV) of 91.22 %, kappa value of 0.904, and an area under the receiver operating characteristic curve (AUC) of 0.973. The subsequent typing tests on our platform for HSV-1 and HSV-2 showed a sensitivity of 100 % (95 % CI: 74.12 %–100 %) and 95.83 % (95 % CI: 86.02 %–99.26 %), respectively. Specificity was 97.85 % (95 % CI: 92.49 %–99.62 %) for HSV-1 and 96.64 % (95 % CI: 85.39 %–98.54 %) for HSV-2. The kappa values were 0.906 for HSV-1 and 0.883 for HSV-2, with PPV of 84.6 % and 97.7 %, and NPV of 100 % and 91.7 %, respectively. Our portable paper strip assay provides a convenient and user-friendly testing option suitable for decentralized settings. This approach has the potential to facilitate early detection and enhance public health efforts in controlling HSV transmission.

Impact of Tobacco Use on Herpes Simplex Virus Infections: Findings From a National Survey.

Herpes simplex virus (HSV) infections, primarily caused by HSV-1 and HSV-2, are prevalent worldwide and carry significant health implications. The impact of tobacco use on HSV infections, however, remains underexplored. This cross-sectional study utilized the National Health and Nutrition Examination Survey (NHANES) database (2009-2016) to investigate the link between Tobacco use and HSV infections among U.S. adults. Smoking status, volume, and serum cotinine levels were analyzed, alongside demographic and behavioral factors. Propensity score matching (PSM) was employed to adjust for confounders such as sexual behavior. Our study involved 5693 participants to explore the relationship between tobacco use and HSV infection. We found that smokers, particularly current smokers, have a significantly increased risk of both HSV-1 and HSV-2 infections compared to non-smokers. Specifically, the adjusted odds ratio (OR) for HSV-1 in current smokers was 1.36 (95% CI: 1.16-1.59, p < 0.001), and for HSV-2, it was 2.37 (95% CI: 1.88-3, p < 0.001). The risk escalates with the intensity of smoking. Elevated serum cotinine levels correlated with an increased risk of HSV infection (HSV-1:1.13 [95% CI:1.09-1.18, p < 0.001]; HSV-2:1.33 [95% CI:1.25-1.41, p < 0.001]). After PSM for factors such as age, gender, sexual behavior, and condom use, these associations remained significant. Tobacco use is significantly associated with an increased risk of HSV infections, highlighting the importance of reducing tobacco exposure in public health strategies against HSV. Further, longitudinal studies are warranted to establish causality and explore underlying mechanisms.

Association of Herpes simplex infection with significantly increased risk of head and neck cancer: real-world evidence of about 500,000 patients.

The role of viral agents in the development of head and neck cancers has remained controversial. While markers of viral origin have been isolated from oral cancer tissues, a causative relationship has yet to be shown. The aim of this study was to evaluate the relationship between head and neck cancers and Herpes simplex virus, one of the most common viral infections of the oral orifice. Here, we conducted a retrospective analysis of two age- and gender-matched cohorts extracted from the real-world database TriNetX on March 10th, 2023, each consisting of 249,272 patients with and without Herpes simplex infections (ICD-10: B00). The diagnoses C00-C14 were analyzed, and risk analysis and Kaplan-Meier survival statics were computed. The strongest association was found for lip cancer (ICD-10: C00) with a hazard ratio [HR (CI 95% low-high)] of 3.08 (1.77-5.35). A significant association with HR of 1.17 (1.02-1.34) was found for the entire group of head and neck cancers. Confounders like smoking and alcohol dependence were considered using propensity score matching. The surprisingly strong correlation with lip, oral cavity, and pharynx neoplasms sheds new light on supposedly harmless herpes simplex infections, suggesting them as a possible new factor for risk stratification.

Recurrent Bilateral Facial Palsy Associated with Herpes Simplex Virus Infection

Bell's palsy is the most common cause of facial paralysis with a lifetime risk of one in 60 in general population. The exact pathophysiology is unknown, but it is suspected to be associated with viral infections such as herpes simplex virus (HSV). Recurrent facial palsy is a rare condition that can be caused by various factors but the cause remains unknown. We report a case of recurrent facial palsy who had antibodies of Lyme immunoglobulin G (IgG), HSV IgG, and IgM.

Study of Hydrolysis Kinetics and Synthesis of Single Isomer of Phosphoramidate ProTide-Acyclovir.

Acyclovir (ACV) is a vital treatment for herpes simplex (HSV) and varicella-zoster virus (VZV) infections that inhibit viral DNA polymerase. Phosphoramidate ProTides-ACV, a promising technology, circumvents the reliance on thymidine kinase (TK) for activation. Twelve novel single isomers of phosphoramidate ProTide-ACV were synthesized. Successful isomer separation was achieved, emphasizing the importance of single isomers in medical advancements. The enzymatic hydrolysis kinetics of the synthesized compounds were investigated by using carboxypeptidase Y (CPY). The results revealed a faster conversion for the isomer Rp- than for the Sp-diastereomer. Hydrolysis experiments confirmed steric hindrance effects, particularly with the tert-butyl and isopropyl groups. Molecular modeling elucidated the mechanisms of hydrolysis, supporting the results of the experiments. This research sheds light on the potential of phosphoramidate ProTides-ACV, bridging the gap in understanding their biological and metabolic properties, while supporting future investigations into anti-HSV activity. Preliminary screening revealed that three of the four single isomers demonstrated superior antiviral efficacy against wild-type HSV-1 compared to acyclovir, with isomer 24a ultimately reducing the viral yield at 200 μM. These findings emphasize the importance of isolating racemic ACV-ProTides as pure single isomers for future drug development.

Genetic defects of brain immunity in childhood herpes simplex encephalitis.

Herpes simplex virus 1 (HSV-1) encephalitis (HSE) is the most common sporadic viral encephalitis in humans. It is life-threatening and has a first peak of incidence in childhood, during primary infection. Children with HSE are not particularly prone to other infections, including HSV-1 infections of tissues other than the brain. About 8-10% of childhood cases are due to monogenic inborn errors of 19 genes, two-thirds of which are recessive, and most of which display incomplete clinical penetrance. Childhood HSE can therefore be sporadic but genetic, enabling new diagnostic and therapeutic approaches. In this Review, we examine essential cellular and molecular mechanisms of cell-intrinsic antiviral immunity in the brain that are disrupted in individuals with HSE. These mechanisms include both known (such as mutations in the TLR3 pathway) and previously unknown (such as the TMEFF1 restriction factor) antiviral pathways, which may be dependent (for example, IFNAR1) or independent (for example, through RIPK3) of type I interferons. They operate in cortical or brainstem neurons, and underlie forebrain and brainstem infections, respectively. Conversely, the most severe inborn errors of leukocytes, including a complete lack of myeloid and/or lymphoid blood cells, do not underlie HSE. Thus congenital defects in intrinsic immunity in brain-resident neurons that underlie HSE broaden natural host defences against HSV-1 from the leukocytes of the immune system to other cells in the organism.

ZC3HAV1 facilitates STING activation and enhances inflammation

Stimulator of interferon genes (STING) is vital in the cytosolic DNA-sensing process and critical for initiating the innate immune response, which has important functions in host defense and contributes to the pathogenesis of inflammatory diseases. Zinc finger CCCH-type antiviral protein 1 (ZC3HAV1) specifically binds the CpG dinucleotides in the viral RNAs of multiple viruses and promotes their degradation. ZAPS (ZC3HAV1 short isoform) is a potent stimulator of retinoid acid-inducible gene I (RIG-I) signaling during the antiviral response. However, how ZC3HAV1 controls STING signaling is unclear. Here, we show that ZC3HAV1 specifically potentiates STING activation by associating with STING to promote its oligomerization and translocation from the endoplasmic reticulum (ER) to the Golgi, which facilitates activation of IRF3 and NF-κB pathway. Accordingly, Zc3hav1 deficiency protects mice against herpes simplex virus-1 (HSV-1) infection- or 5,6-dimethylxanthenone-4-acetic acid (DMXAA)-induced inflammation in a STING-dependent manner. These results indicate that ZC3HAV1 is a key regulator of STING signaling, which suggests its possible use as a therapeutic target for STING-dependent inflammation.