Simplex Virus Research Articles

Etiologies and Demographic Distribution of Uveitis in a Referral Center in Iraq

Purpose: To determine the etiologies and demographic distribution of uveitis in a referral center in Baghdad, Iraq, and to compare the results with a similar study done in the same center in 2014. Study Design: Descriptive observational study. Place and Duration of Study: Ibn Al-Haitham Teaching Eye Hospital, Iraq, from January 2019 to June 2022. Patients and Methods: Two hundred and fourteen patients with uveitis were included. They underwent complete ocular and relevant systemic examination. Data was collected and analyzed using descriptive statistics. Comparison was done with the data retrieved from 2014. Results: Out of 264 patients, only 214 (81%) completed follow up. Others did not show up again due to Corona virus Pandemic. There were 122 (57%) females, 95 (44.3%) were unilateral, 62 (28.9%) were granulomatous, 62 (28.9%) were anterior, 42 (19.6%) were intermediate, 4 (1.8%) were posterior and 106 (49.7%) were panuveitis cases. Cause was identified in 161 (75.3%) patients while 53 (24.7%) were considered idiopathic. Out of 214 patients, 84 (39.2%) were due to infectious causes like tuberculosis, herpes (herpes zoster or simplex viruses), and toxoplasmosis. On the other hand, 130 (60.7%) cases were non-infectious for example, Vogt-Koyanagi-Harada disease, Behcet disease, connective tissue diseases such as Ankylosing Spondylitis, or idiopathic. Conclusion: A minor change was found from the 2014 study to 2023. Tuberculosis is now the most common cause of infectious uveitis instead of Toxoplasmosis. Furthermore, Idiopathic, Vogt-Koyanagi-Harada, and Behcet disease are the commonest causes of non-infectious uveitis.

Painful facial, oral, and genital ulcers

Painful facial, oral, and genital ulcers

Physical Activity Increases Immunity to COVID-19 Infection.

Coronavirus are truly one of the maximum critical fantastic-stranded non-segmented RNA viruses, named after the approximately 126-nm-diameter envelope around the nucleic acid-protein complicated. The virus causes significant harm to human fitness, including direct injury to the respiratory system, immune system compromise, worsening of the underlying clinical conditions, and eventually systemic failure and death. Exercise affects the immune system's antiviral mechanisms. Modest exercise, done before or after infection, improves morbidity and mortality to the contamination, according to animal investigations using influenza and simplex virus in the respiratory tract. Moreover, preclinical research has demonstrated that overtraining has a negative impact on the body's response to viral infections. Follow-up research has shed some light on the mechanisms underlying these discoveries. Through the activation of muscle protein synthesis, physical activity (PA) and exercise are essential for maintaining muscle mass. On the other hand, a lack of muscle contractile activity throughout the country of no exercise, particularly in elderly people, is a major contributor to anabolic rigidity and muscle atrophy.

Assessment of antimicrobial, cytotoxicity, and antiviral impact of a green zinc oxide/activated carbon nanocomposite

This work deals with the synthesis of zinc oxide nanoparticles/activated carbon (ZnO NPs/AC) nanocomposites with different weight ratios (3:1, 1:1, and 1:3), where the antimicrobial, antiviral, and cytotoxicity impact of the formulated nanocomposites were evaluated versus the crude ZnO and AC samples. The formula (3:1; designated Z3C1) exhibited the utmost bactericidal effect against Gram positive group, unicellular and filamentous fungi. Regarding Gram negative group, the sample (Z3C1) was remarkably effective against Klebsiella pneumonia, unlike the case of Escherichia coli. Moreover, the whole samples showed negligible cytotoxicity against the human WI38 cell line, where the most brutality (4%) was exerted by 1000 µg/mL of the formula (Z1C3). Whilst, the formula (Z3C1) exerted the apical inhibition impact against Herpes simplex (HSV1) virus. Consequently, the synthesized (Z3C1) nanocomposite was sorted out to be fully characterized via different physicochemical techniques including FTIR, XRD, SEM, TEM, Zeta potential, TGA, and BET. XRD indicated a predominance of the crystalline pattern of ZnO NPs over the amorphous AC, while the FTIR chart confirmed an immense combination between the ZnO NPs and AC. SEM, TEM, and size distribution images illustrated that the fabricated ZnO NPs/AC was in the nanoscale size swung from 30 to 70 nm. The distinctive surface area of composite material, recording 66.27 m2/g, clearly disclosed its bioactivity toward different bacterial, fungal, and virus species.

Herpes simplex Virus Pneumonitis in an Acute/Subacute Paracoccidioidomycosis Patient With Malabsorption Syndrome. Case-Report and Literature Review.

Paracoccidioides sp.-Herpes simplex virus (HSV) co-infection was not reported until now and malabsorption syndrome is a rare complication of the acute/subacute form (AF) of paracoccidioidomycosis (PCM), characterized by life-threatening abnormalities, such as fat and protein loss, lymphopenia, ascites, and intense immunosuppression. A 21-year-old woman presented the PCM AF with intense involvement of the abdominal and intestinal lymphoid organs, which leads to the malabsorption syndrome and severe immunosuppression. This patient developed a fatal-disseminated HSV infection associated with the paracoccidioidal disease. This case demonstrates that, in addition to the antigen-specific immunosuppression, some PCM patients can present a generalized cell-mediated immune depression and endogenous infection of latent microorganisms. On the best of our knowledge, this is the first report of an association between PCM and HSV infection.

The Screening of Rubella Virus, Cytomegalovirus, Hepatitis B Virus, and Toxoplasma gondii Antibodies in Prepregnancy and Reproductive-Age Women in Tabriz, Iran.

Objectives The organisms of Toxoplasma gondii, Rubella virus, Cytomegalovirus, and Herpes simplex virus as an acronym of TORCH are major pathogens in prepregnancy and reproductive-age women. These microorganisms are considered a serious problem and cause 2-3% of all birth defects in the fetus. Our study was aimed at screening the seroprevalence of TORCH antibodies among prepregnancy and reproductive-age women in Tabriz, Iran. Design and Setting. This study was carried out in 2726 prepregnancy and reproductive-age women, who were referred to the laboratory for prenatal TORCH screening. To detect the presence of IgG, IgM antibodies and Hepatitis B surface antigen against these microorganisms were carried out using a chemiluminescence immunoassay analyzer (CLIA). Results In the current study, the rates of anti-Toxoplasma gondii IgG, anti-Rubella virus IgG, and anti-Cytomegalovirus IgG were found in 722 cases (26.5%), 2579 cases (94.6%0), and 2718 cases (99.7%), respectively. Moreover, the rates of anti-Toxoplasma gondii IgM, anti-Rubella virus IgM, and anti-Cytomegalovirus IgM were discovered in 10 cases (0.4%), 13 cases (0.5%), and 16 cases (0.6%), respectively. The Hepatitis B surface antigen was found in 32 cases (1.2%). The dissemination of positive TORCH in various ages was different (P < 0.05). Conclusions In our study, the seroprevalence of acute TORCH infections was relatively low. Due to the probability of vertical transmission to the fetus during pregnancy and the unpleasant complication of these pathogens, it is essential to be screened for detection of specific IgG and IgM antibodies in reproductive ages.

937. A Clinical Prediction Tool to Determine Risk of Infection in the First Year Following Heart Transplant

BackgroundInvasive infection is a dangerous complication of heart transplant (HT). No objectively-defined set of risk factors has been established which can reliably predict infection in this population. The aim of this study was to develop a clinical prediction model for use at one month post-HT with the ability to predict serious infection in the first year.MethodsA retrospective cohort study of all HT recipients at a single center between 2000 and 2018 was performed, excluding dual-organ recipients, those who died within one month of HT, and those with insufficient data. The composite endpoint included cytomegalovirus infection (CMV), herpes simplex (HSV) or varicella zoster virus infection (VZV), blood stream infection (BSI), and invasive fungal infection (IFI). The follow-up period extended from 1 month to 1 year post-HT. A least absolute shrinkage and selection operator (LASSO) regression model was fit using 13 candidate variables. A C-statistic, calibration curve, and Brier score were used to assess model performance.Results375 patients were analyzed; 93 outcomes occurred (65 CMV, 3 HSV, 2 VZV, 28 BSI, and 15 IFI). 12 of 13 variables remained in the final model: year of transplant, age at transplant, ischemic cardiomyopathy, diabetes, immune-mediating disease, need for renal replacement therapy in first month, CMV risk status (high, intermediate, low) derived from donor-recipient serology, use of basiliximab induction, use of cytolytic agent in first month, use of ritixumab in first month, rejection treated with high-dose steroids in first month, lymphocyte count under 0.75 x103cells/µL at 1 month, and inpatient status at 1 month. The C-statistic was 0.82 and Brier score 0.142. The calibration curve is shown in Figure 1. Figure 1. Calibration plot Actual versus predicted probability of infection by 1 year. Gray line = ideal Dotted line = smoothed non-parametric calibration curveConclusionThis model synthesizes multiple highly-relevant clinical and laboratory parameters, available at 1 month post-HT, into a unified, objective, and clinically-useful prediction tool for the occurrence of serious infection in the first post-transplant year. Good discrimination and calibration are demonstrated. External validation is required before generalized use.Disclosures Jennifer Chow, M.D., M.S., Merck (Grant/Research Support)Takeda (Grant/Research Support) David R. Snydman, MD, Merck (Consultant, Advisor or Review Panel member, Research Grant or Support)Takeda (Shire) (Advisor or Review Panel member)

Acute retinal necrosis caused by co-infection with multiple viruses in a natalizumab-treated patient: a case report and brief review of literature

BackgroundAcute retinal necrosis is considered a rare infectious uveitis. This condition is usually caused by varicella-zoster virus or herpes simplex virus. Acute retinal necrosis caused by co-infection with multiple viruses is extremely rare. Herein, we report a case of acute retinal necrosis caused by co-infection with herpes simplex virus (type I and II) and varicella-zoster virus (VZV) in a natalizumab-treated patient due to multiple sclerosis.Case presentationAn adult man presented with a complaint of decreased vision of the right eye from 12 days ago. He was a known case of multiple sclerosis receiving natalizumab. Examination of the right eye revealed severe conjunctival injection, fine diffuse keratic precipitates, 3 + anterior chamber and vitreous cells, elevated intraocular pressure (26 mmHg), a blurred optic disk with hemorrhagic patches, and occlusive vasculitis plus confluent necrotizing patches in the peripheral retina compatible with diagnosis of acute retinal necrosis. He underwent anterior chamber and vitreous tap, and real-time PCR detected HSV I & II and VZV on the vitreous specimen. A second PCR showed the same result. After neurological consultation, natalizumab was discontinued and intravenous acyclovir was started followed by oral acyclovir and oral prednisolone to control the disease, which was successful.ConclusionsAlthough rare, multiple-viral infection should be considered in the physiopathology of acute retinal necrosis, especially in immunosuppressed patients.

Acute Retinal Necrosis (ARN): Time is Retina (A Case Study)

Acute retinal necrosis (ARN) is an inflammatory condition characterized by a peripheral retinal necrosis due to an infection with varicella-zoster virus or herpes simplex virus. It is commonly seen in immunocompetent adults and is known for its rapid evolution and poor prognosis. Our case study illustrates the gravity of this condition with an extremely rapid ARN that was hard to diagnose.

Design and evaluation of a multiplex vesicular rash PCR for the detection of varicella zoster virus and herpes simplex virus

Varicella zoster virus (VZV) typically infects the skin leading to chickenpox (varicella) and herpes zoster whereas herpes simplex virus 1 and 2 (HSV-1/-2) often affect the mucosa forming herpes labialis and genital herpes. However, in eczema herpeticum and herpes gladiatorum, HSV infections occur on the skin. The cutaneous infections with VZV or HSV often present similar clinical manifestations causing trouble in differentiation.

Is There Any Relation between Serum Levels of Interleukin-10 and Neurophysiological Abnormalities in Bell's Palsy?

Background:Bell’s palsy is the most common cause of peripheral facial palsy. The etiology and treatment of Bell’s palsy are still controversial. Previous studies emphasize the role of herpes simplex and herpes zoster viruses in this ailment. The role of Interleukin-10 (IL-10) in Bell’s palsy is yet unknown, and few studies have shed light on the matter. This study intended to assess the prognostic value of IL-10 and its relation to the intensity of electrodiagnostic abnormalities and evaluate its potential use as a factor for judging the need for medical or surgical interventions.Materials and Methods:30 patients in the acute phase of Bell’s palsy participated in this study. Peripheral blood samples were obtained for IL-10 assessment within the first 72 hours (before commencing treatment), and a nerve conduction study (NCS) was performed six days after symptom onset.Results:There was no significant correlation between IL-10 serum levels and the severity of nerve conduction pathology in Orbicularis oculi and Orbicularis oris muscles. Also, IL-10 serum levels did not show any meaningful relationships with participants’ age, gender, or symptoms.Conclusion:The IL-10 serum levels are not relevant to the pathology of Bell’s palsy, and the assessment of IL-10 serum levels cannot be used as an alternative to NCS for evaluating the severity of acute Bell’s palsy.

HSV-1 Oncolytic Viruses from Bench to Bedside: An Overview of Current Clinical Trials.

Simple SummaryOncolytic Herpes simplex virus-1 (HSV-1) offers the dual potential of both lytic tumor-specific cell killing and inducing anti-tumor immune responses. The HSV-1 genome can be altered to enhance both components and this may be applicable for the treatment of a broad range of cancers. Several engineered oncolytic viruses based on the HSV-1 backbone are currently under investigation in various clinical trials, both as single agents and in combination with various immunomodulatory drugs.Herpes simplex virus 1 (HSV-1) provides a genetic chassis for several oncolytic viruses (OVs) currently in clinical trials. Oncolytic HSV1 (oHSV) have been engineered to reduce neurovirulence and enhance anti-tumor lytic activity and immunogenicity to make them attractive candidates in a range of oncology indications. Successful clinical data resulted in the FDA-approval of the oHSV talimogene laherparepvec (T-Vec) in 2015, and several other variants are currently undergoing clinical assessment and may expand the landscape of future oncologic therapy options. This review offers a detailed overview of the latest results from clinical trials as well as an outlook on newly developed HSV-1 oncolytic variants with improved tumor selectivity, replication, and immunostimulatory capacity and related clinical studies.

ROLE OF IMAGING IN DIAGNOSIS OF INTRACRANIAL INFECTIONS- LITERATURE REVIEW

Neuroimaging performs an essential position in the analysis and diagnostic choice making in infectious illnesses of the world. The overview summarizes imaging findings and latest advances in the diagnosis of pyogenic brain abscess, ventriculitis, viral diseases which includes distinguished and emerging viruses, and opportunistic infections. For each circumstance, the ensuing therapeutic steps are presented. In instances of typical meningitis, cranial computed tomography (CT) seems to be enough for clinical control to exclude acute cerebral edema, hydrocephalus, and pathology involving the base of the skull. Magnetic resonance imaging (MRI) is advanced in depicting complications like subdural and epidural empyema and vasculitic complications considerably on FLAIR (fluid-attenuated inversion healing)-weighted pics. The more recent technique of diffusion-weighted imaging (DWI) suggests early parenchymal headaches of meningitis in advance and with greater readability and is of assist in differentiation of pyogenic abscess (PA) from ring enhancing lesions of other etiology. Proton magnetic resonance spectroscopy (PMRS) seems to produce unique top patterns in instances of abscess. The presence of lactate cytosolic amino acids and absence of choline appears to signify PA. Additionally in instances of suspected opportunistic infection because of toxoplasma DWI can be of very helpful inside the differentiation from lymphoma, showing no limit of water diffusion. In patients with herpes simplex and extra exceptional viruses like West Nile and Murray Valley virus, DWI lets in advance lesion detection and better therapeutic intervention with virustatic tablets.

Evaluation of Some Biological Activities of Phialosimplex asmahalo

Phialosimplex asmahalo is an obligate halophilic fungus that requires at least 5 % (w/v) sodium chloride for growth. It was previously isolated and identified. The ethyl acetate extract ofPhialosimplex asmahalo was fractionated and three compounds 1, 3, and 6 were purified. In this studypure compounds of Phialosimplex asmahalo were evaluated for their anti-diabetes, anti-inflammatory, antiviral and hepatoprotective activities. Compounds 3 and 6 have anti-diabetic activities with IC50 47.03 and 82.3 respectively; whereas compound 1 has no anti-diabetic activity. Compounds 3 and 6 have anti-inflammatory activities with IC50 125 and 294 respectively; whereas compound 1 has no anti-inflammatory activity. Compound 3 has antiviral activity against Hepatitis A virus and Herpes Simplex type 1 virus in a percentage of 24.7 and 10.2 respectively. Compound 6 has antiviral activity against Hepatitis A only with a percentage of 11.3. Compound 1 has no antiviral activity against Hepatitis A virus and Herpes Simplex type 1 virus. Compounds 1 and 3 have hepatoprotective activities percentage 7.1 and 23.6 respectively; whereas compound 6 has no hepatoprotective activity.

Does HSV in Lavage Fluid of Ventilated Patients Warrant Antiviral Treatment

In critically ill, mechanically ventilated patients, herpes simplex virus (HSV) can frequently be detected in the respiratory tract. Whether this

Etiology and molecular-epidemiological characteristics of viral meningo-encephalitis in Zhejiang province, 2002-2018

Objective: To understand the pathogens and molecular-epidemiologic characteristics of viral meningo-encephalitis in Zhejiang province during 2002 to 2018. Methods: All the samples were collected from suspected patients admitted to the hospitals under the monitoring program. Of the total samples, 2 173 were cerebrospinal fluids while the other 455 were stool specimens. Cerebrospinal fluid (CSF) samples were subject to real-time qPCR for the detection of Human enterovirus (HEV), Mumps virus (MuV), Herpes simplex virus (HSV), Cytomegalovirus (CMV) and Japanese encephalitis virus (JEV). Stool sample were subject to real-time qPCR for HEV. ELISA was used to detect the IgM antibodies in CSF, in the 5 kinds of virus mentioned above. VP1 genes from all RNA-positive specimen were amplified, sequenced, for typing and for evolution analysis. Results: 871 (40.1%) of the 2 173 samples were detected as HEV nucleic acid positive during 2002 to 2018. 654 (38.1%) of the 1 718 CSF sample were HEV nucleic acid positive while 217 (47.7%) of the 455 stool sample were HEV nucleic acid positive. Among the total positive nucleic acid sample, 670 of them were VP1 sequence positive, including 5 HEV-A and 665 HEV-B. There were 23 HEV serotypes, including Coxsackievirus (CV) CVA4, CVA6, CVA9, CVA10, CVB1-5, Echovirus (EchoV; E) E3, E4, E6,E7, E9, E11, E14, E16, E18, E21, E25, E30, E33 and EV-71. The top three serotypes went to E30, E6 and CVB5. These three serotypes presented enhanced viral activity in every several years. 795 CSF samples were detected as virus nucleic acid positive, including 374 HEV, 6 MuV, 5 HSV and 5 CMV, from 2012 to 2015 and in 2018. 5 kinds of IgM antibodies were detected simultaneously in 368 CSF samples, including 2 HEV positive, 6 JEV positive and 1 MuV positive for 5 viruses, respectively. Except for EV-71, there were 517 EchoV and 152 CV viruses presented, with the ratio of 3.4∶1. These two kinds of viruses alternately changed for each predominant epidemic strains in every 3-5 years. Based on VP1, results from the phylogenetic tree showed that HEV from Zhejiang province clustered into HEV-A and HEV-B clades respectively. E30 developed both h and i sub-genotypes. Conclusions: HEV-B seemed the main pathogen for viral meningo-encephalitis in Zhejiang province. Ratio of positive detection on EchoV was significantly higher than that on CV. These two kinds of virus alternately presented changing tendency in every several years. Predominant epidemic strains E30, CVB5 and E6 were presenting enhanced viral activity, also in every several years. High correlation was found in both HEV viral activity from the surveillance sites and in time line of the viral meningo-encephalitis outbreaks.

Intrinsically disordered regions are abundant in simplexvirus proteomes and display signatures of positive selection.

Whereas the majority of herpesviruses co-speciated with their mammalian hosts, human herpes simplex virus 2 (HSV-2, genus Simplexvirus) most likely originated from the cross-species transmission of chimpanzee herpesvirus 1 to an ancestor of modern humans. We exploited the peculiar evolutionary history of HSV-2 to investigate the selective events that drove herpesvirus adaptation to a new host. We show that HSV-2 intrinsically disordered regions (IDRs)—that is, protein domains that do not adopt compact three-dimensional structures—are strongly enriched in positive selection signals. Analysis of viral proteomes indicated that a significantly higher portion of simplexvirus proteins is disordered compared with the proteins of other human herpesviruses. IDR abundance in simplexvirus proteomes was not a consequence of the base composition of their genomes (high G + C content). Conversely, protein function determines the IDR fraction, which is significantly higher in viral proteins that interact with human factors. We also found that the average extent of disorder in herpesvirus proteins tends to parallel that of their human interactors. These data suggest that viruses that interact with fast-evolving, disordered human proteins, in turn, evolve disordered viral interactors poised for innovation. We propose that the high IDR fraction present in simplexvirus proteomes contributes to their wider host range compared with other herpesviruses.

Epidemiological characteristics of herpes simplex virus

Herpes simplex virus type 1 (HSV-1) commonly causes orolabial ulcers. However, HSV-1 has become an increasing cause of genital infection in recent years and found to have close relationship associated with Alzheimer′s disease. HSV infection is one of the most common sexually transmitted diseases. It has been received renewed attention in recent years, due to improvements in the understanding of the epidemiological synergy between HSV and other severe diseases, including HIV, sexually transmitted infections, and even neurocognitive impairment. In the context of global renewed attention and responses to HSV infection, we summarize the epidemic of HSV infection at home and abroad in this review, to provide an overview of the data available on HSV infections situation, trends and responses. Key words: Herpes simplex virus; Diagnosis and detection methods; Epidemiological analysis

TORCH screening used appropriately in China?\u2500three years results from a teaching hospital in northwest China

ObjectivesTORCH infections caused by Toxoplasma gondii (TOX), rubella virus (RV), cytomegalovirus (CMV) and herpes simplex virus 1,2 (HSV-1,2) are associated with congenital anomalies. The study aimed to analyze the characteristics of TORCH screening in reproductive age women.MethodsA total of 18,104 women (2015–2017) from a teaching hospital in Xi’an, China, were enrolled in the study. The characteristics of TORCH screening, i.e., the application of TORCH test, the seroprevalence, the impact of age, periods of gestation and woman with bad obstetric history (BOH) on the serological data were investigated.ResultsIn the study, 319 women (1.76%) performed dynamic TORCH test. 51.66, 20.44 and 3.83% of the population did the test in the pre-gestation period, the first and third trimester, respectively. Quite a few pre-gestation women (29.74%) ignored screening of IgG antibodies. The overall IgG/IgM seropositvity of TOX, RV, CMV, HSV-1 and HSV-2 was 4.35%/0.35, 90%/0.63, 96.79%/0.97, 81.11%/0.14 and 6.1%/0.19%, respectively. The age-specific distributions and periods of gestation had no significant effect on the seroprevalence of TORCH agents, p>0.05. However, BOH was significantly associated with higher seropositvity of IgM (RV, CMV, HSV-1 and HSV-2) and IgG (CMV and HSV-1) antibodies, p < 0.05.ConclusionIn Xi’an region, more attentions should be paid to TOX, CMV, HSV-2 and the women with BOH for TORCH screening. Meanwhile, a greater emphasis needs to be placed on TORCH test used inappropriately in China.

Development of a Reporter System Monitoring Regulated Intramembrane Proteolysis of the Transmembrane bZIP Transcription Factor ATF6α.

When endoplasmic reticulum (ER) functions are perturbed, the ER induces several signaling pathways called unfolded protein response to reestablish ER homeostasis through three ER transmembrane proteins: inositol-requiring enzyme 1 (IRE1), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6). Although it is important to measure the activity of ATF6 that can indicate the status of the ER, no specific cell-based reporter assay is currently available. Here, we report a new cell-based method for monitoring ER stress based on the cleavage of ATF6α by sequential actions of proteases at the Golgi apparatus during ER stress. A new expressing vector was constructed by using fusion gene of GAL4 DNA binding domain (GAL4DBD) and activation domain derived from herpes simplex virus VP16 protein (VP16AD) followed by a human ATF6α N-terminal deletion variant. During ER stress, the GAL4DBD-VP16AD(GV)-hATF6α deletion variant was cleaved to liberate active transcription activator encompassing GV-hATF6α fragment which could translocate into the nucleus. The translocated GV-hATF6α fragment strongly induced the expression of firefly luciferase in HeLa Luciferase Reporter cell line containing a stably integrated 5X GAL4 site-luciferase gene. The established double stable reporter cell line HLR-GV-hATF6α(333) represents an innovative tool to investigate regulated intramembrane proteolysis of ATF6α. It can substitute active pATF6(N) binding motif-based reporter cell lines.