Reactivation Of Latent Varicella Zoster Virus Research Articles

Lipo-pam™ adjuvanted herpes zoster vaccine induces potent gE-specific cellular and humoral immune responses

Herpes zoster (HZ), also known as shingles, is caused by the reactivation of latent varicella-zoster virus (VZV). Decreased VZV-specific T-cell immune responses significantly contribute to the development of HZ. Shingrix is a recombinant zoster vaccine that is currently used to prevent HZ. However, Shingrix has high reactogenicity and pain at the injection site due to QS21, one of the adjuvant components. In this study, we developed a new herpes zoster vaccine formulation called CVI-VZV-001, containing gE protein and a novel liposome-based adjuvant Lipo-pam™, which consists of two TLR agonists. We evaluated the immunogenicity of CVI-VZV-001 in mouse and rabbit models. CVI-VZV-001 elicited robust gE-specific T-cell immune responses and gE-specific antibody production. Specifically, CVI-VZV-001 induced polyfunctional CD4+ T cell populations that secrete multiple cytokines. Furthermore, CVI-VZV-001 sustained the gE-specific immune responses for up to six months after immunization. To ensure CVI-VZV-001’s safety for further development, we conducted a good laboratory practice (GLP) toxicity test, which confirmed that CVI-VZV-001 is safe for use. At present, CVI-VZV-001 is undergoing phase I clinical trials. This study suggests that CVI-VZV-001 can be a potent candidate for the HZ vaccine with high immunogenicity and safety.

BioNTech COVID-19 (BNT162b2) Vaccination and Varicella Zoster Reactivation: A Comprehensive Cross-sectional Study.

Herpes zoster (HZ) results from reactivation of latent varicella-zoster virus. Recent observations have suggested that HZ is associated with vaccination against COVID-19. To investigate the association between the vaccine and HZ severity, a single-centre, cross-sectional study of all patients diagnosed with HZ and 2 control diagnoses (cellulitis and bone fractures), between 2017 and 2021, was performed. Hospital visits and hospitalization rates were compared. All medical records of patients diagnosed with HZ in the first year after the COVID-19 vaccination campaign began were reviewed, in order to generate a retrospective cohort comparing vaccinated and unvaccinated patients with HZ. All participants had received the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine. During the study period, 2,413 patients were diagnosed with HZ, and when normalized to control diagnoses the number of cases remained stable. The retrospective cohort included 365 patients. A multivariate analysis controlling for sex, age, autoimmune diseases, malignancies, and immunosuppressive therapy showed higher admission rates in vaccinated compared with unvaccinated individuals (odds ratio (OR) 2.75, 95% CI 1.27-5.96, p = 0.01). However, matching techniques and stratification by age, used to better control for confounders, invalidated these findings. No differences were observed in other variables indicative of disease severity (hospital stay length and complications). In conclusion, COVID-19 vaccination was not found to be associated with an increased risk of HZ-related admission and complications.

Progressive shingles in a toddler due to reactivation of Varicella Zoster vaccine virus four days after infection with SARS-CoV-2; a case report

BackgroundHerpes zoster (HZ) is the clinical syndrome associated with reactivation of latent varicella-zoster virus (VZV). Several factors have been implicated to promote VZV reactivation; these include immunosuppression, older age, mechanical trauma, physiologic stress, lymphopenia, and more recently, infection with severe acute respiratory syndrome coronavirus-2 (SARS- CoV-2). Recent reports suggest an increase in the number of HZ cases in the general population during the global COVID-19 pandemic. However, it is unknown what proportion of HZ during the pandemic is due to reactivation of wild-type or vaccine-strain VZV.CaseHere we report the first known case of HZ concomitant with SARS-CoV2 infection in a 20-month-old female who was treated with a single dose of dexamethasone, due to reactivation of the vaccine-type strain of VZV after presenting with a worsening vesicular rash.ConclusionIn this case, we were able to show vaccine-strain VZV reactivation in the context of a mild acute symptomatic COVID-19 infection in a toddler. Being able to recognize HZ quickly and effectively in a pediatric patient can help stave off the significant morbidity and mortality associated with disease process.

Immunogenicity in Mice Immunized with Recombinant Adenoviruses Expressing Varicella-Zoster Virus Envelope Glycoprotein E.

Herpes zoster (HZ) is a disease caused by the reactivation of latent varicella-zoster virus (VZV). The subunit vaccine, Shingrix®, and live attenuated vaccine, Zostavax®, could be used as an HZ vaccine that prevents HZ from being developed due to the reactivation of latent VZV in the sensory ganglia due to aging, stress or immunosuppression. In this study, the recombinant adenoviruses rChAd63/gE expressing glycoprotein E (gE) of VZV based on chimpanzee adenovirus serotype 63 (ChAd63) were constructed and investigated for the immunogenicity of different immune pathways in C57BL/6 mice. The results showed similar CD4+ T and CD8+ T cell responses to Shingrix® were induced in mice vaccinated using rChAd63/gE via different immune pathways. This study elucidates that recombinant adenoviruses expressing VZV gE could be appropriate for further development as a new HZ vaccine candidate via different immune pathways.

Hospitalization burden related to herpes zoster infection during the COVID-19 pandemic in Spain (2020-2021)

ABSTRACT Varicella-Zoster Virus (VZV) belongs to the family Herpesviridae. Herpes zoster (HZ) is caused by reactivation of latent VZV. It is associated with risk factors such as immunosenescence, immunosuppressive pathologies and pharmacological treatments. Patients with these risk factors are more likely to be hospitalized. Increases in HZ hospitalizations have been reported in many countries in recent years. The objective of this study is to estimate hospitalization rates, mortality rates and costs due to HZ during the worst years of the COVID-19 pandemic in Spain (2020–2021). This is a descriptive study based on an analysis of information from the Minimum Basic Dataset and coded according to the Spanish version of the 10th International Classification of Diseases (ICD-10-CM). Hospitalization, mortality and case-fatality rates, and median length of hospitalization were calculated.. The hospitalization rate was 14.4 cases per 100,000 inhabitants, and the mortality rate was 1.3 cases per 100,000 inhabitants. Both increased considerably with age. In this time period, 92.3% of the registered cases were people over 50 years of age. Nevertheless, during the COVID-19 pandemic period, hospitalization rate decreased and the mortality rate increased from previous years. HZ hospitalization and mortality rates are relevant issues in the public health of older people. It is highly recommended to evaluate new vaccination strategies against VZV to include the HZ vaccine for health care for elderly people, as well as to reduce the disease burden and associated risk factors. The estimation of HZ disease hospitalization costs were €100,433,904.

Homoeopathic Treatment of Childhood Herpes Zoster—A Case Series

Abstract Background Herpes zoster (HZ) is a relatively rare infectious disease in the paediatric population as compared to adults, occurring due to the reactivation of latent varicella-zoster virus that persists in the posterior root ganglion. HZ can develop any time after the primary infection and is characterised by grouped vesicular rashes limited to single dermatome. Diagnosis is based on a distinct clinical appearance of HZ. Its clinical course is variable, and it requires prompt medical treatment to prevent the complications. In conventional method, antiviral and other treatment modalities are available; however, these are fraught with potentially severe side effects and is expensive that demands an alternative method of treatment. Methods A case series of three children with HZ treated with individualised homeopathy is presented here. The cases are reported according to HOM-CASE guidelines and followed up with photographic documentation. The Modified Naranjo Criteria for Homeopathy (MONARCH) inventory was used as a tool for assessing the causal relationship between homeopathic intervention and clinical outcome. Results All cases of HZ were successfully cured with individualised homoeopathy within 10 days without any complication. Individual curative response of the homoeopathic medicine in each case was assessed through MONARCH which demonstrated a positive causal attribution of homeopathy. Conclusion Successful results of this case series suggest a positive response of individualised homeopathic medicines in the treatment of childhood HZ. The remissions of the HZ lesion presented in this case series may be attributed to homeopathic medicines in each case. Hence, this case series could serve as a basis for further research into the role of individualised homeopathic medicine in the treatment of childhood herpes zoster.

Treatment with Brivudine in Immunocompromised Pediatric Patients with Herpes Zoster

Introduction: Herpes zoster (HZ) is caused by endogenous reactivation of latent varicella-zoster virus (VZV) that persists in sensory ganglia after primary infection. The incidence and severity of HZ increase during immunosuppression. Especially, immunocompromised patients are at high risk of developing a cutaneous rash and suffering from delayed healing of lesions. Bromovinyl deoxyuridine (brivudine), one of the most potent oral inhibitors of VZV replication, is widely used in the therapy of HZ in adult patients, particularly in Europe. In this study, we investigated the efficacy of brivudine in immunocompromised children to provide an outpatient treatment option. Methods: In this retrospective study, we included 64 immunocompromised pediatric patients with a median age of 14 years. Forty-seven patients received immunosuppressive therapy as part of hematopoietic stem cell transplantation and 17 patients as part of chemotherapy. Primary diagnosis was made clinically by examining the nature and the localization of the skin lesions. Laboratory confirmation was conducted based on the detection of VZV DNA in vesicle fluid and blood samples. Brivudine was administered orally at a single dose of 2 mg/kg per day. We monitored the patients’ response for the full time of treatment and observed the time of full crusting of lesions, loss of crusts, and any adverse effects that occurred. Results: Patients received medication for 7–21 days (median: 14 days). All children responded promptly to antiviral treatment and recovered completely from their HZ infections without complications. Crusting of lesions was reached after 3–14 days (median: 6 days). Full healing of skin lesions was ascertained within 7–21 days (median: 12 days). Overall, brivudine therapy was well tolerated. No clinical side effects during or after the treatment were observed. High compliance was achieved due to the once-daily dosing regimen. All patients were treated in an outpatient manner. Conclusion: Oral brivudine was a very effective and well-tolerated therapy in immunocompromised children with HZ infection. The oral administration offers the potential for outpatient treatment of HZ in these patients.

In Silico Design and Experimental Validation of Novel Oxazole Derivatives Against Varicella zoster virus.

Varicella zoster virus (VZV) infection causes severe disease such as chickenpox, shingles, and postherpetic neuralgia, often leading to disability. Reactivation of latent VZV is associated with a decrease in specific cellular immunity in the elderly and in patients with immunodeficiency. However, due to the limited efficacy of existing therapy and the emergence of antiviral resistance, it has become necessary to develop new and effective antiviral drugs for the treatment of diseases caused by VZV, particularly in the setting of opportunistic infections. The goal of this work is to identify potent oxazole derivatives as anti-VZV agents by machine learning, followed by their synthesis and experimental validation. Predictive QSAR models were developed using the Online Chemical Modeling Environment (OCHEM). Data on compounds exhibiting antiviral activity were collected from the ChEMBL and uploaded in the OCHEM database. The predictive ability of the models was tested by cross-validation, giving coefficient of determination q2 = 0.87-0.9. The validation of the models using an external test set proves that the models can be used to predict the antiviral activity of newly designed and known compounds with reasonable accuracy within the applicability domain (q2 = 0.83-0.84). The models were applied to screen a virtual chemical library with expected activity of compounds against VZV. The 7 most promising oxazole derivatives were identified, synthesized, and tested. Two of them showed activity against the VZV Ellen strain upon primary in vitro antiviral screening. The synthesized compounds may represent an interesting starting point for further development of the oxazole derivatives against VZV. The developed models are available online at OCHEM http://ochem.eu/article/145978 and can be used to virtually screen for potential compounds with anti-VZV activity.

Selective retention of virus-specific tissue-resident T cells in healed skin after recovery from herpes zoster

Herpes zoster is a localized skin infection caused by reactivation of latent varicella-zoster virus. Tissue-resident T cells likely control skin infections. Zoster provides a unique opportunity to determine if focal reinfection of human skin boosts local or disseminated antigen-specific tissue-resident T cells. Here, we show virus-specific T cells are retained over one year in serial samples of rash site and contralateral unaffected skin of individuals recovered from zoster. Consistent with zoster resolution, viral DNA is largely undetectable on skin from day 90 and virus-specific B and T cells decline in blood. In skin, there is selective infiltration and long-term persistence of varicella-zoster virus-specific T cells in the rash site relative to the contralateral site. The skin T cell infiltrates express the canonical tissue-resident T cell markers CD69 and CD103. These findings show that zoster promotes spatially-restricted long-term retention of antigen-specific tissue-resident T cells in previously infected skin.

Ramsay-Hunt syndrome in HIV patient

Introduction Ramsay-Hunt syndrome type (SRH) type II is defined by the combination of herpes zoster oticus to acute peripheral facial nerve paralysis, described in 1907 by James Ramsay Hunt. Reactivation of latent varicella-zoster virus in the geniculate ganglion of the facial nerve will cause SRH, resulting in inflammation, edema, and compression of the VII cranial pair. However, nerve involvement, and in turn the development of SRH, manifests in less than 1% of infected patients. It is the second most common cause of atraumatic peripheral facial palsy (PFP) and has an incidence of 5 cases/100,000 people, with no sex predilection. Currently, SRH is classically described as a triad of otalgia, ipsilateral facial paralysis, and vesicles near the ear and ear canal; however, motor, sensory, and autonomic impairment when combined result in diverse neurological damage and may cause different symptoms, its diagnosis is mainly clinical. Goal To report the case of an HIV patient associated with SHR, seen by IIER between May and June/2022. Case Report Male, 49 years old, sought care on 05/20/22 in a hospital with complaints of vertigo and intense headache, associated with nausea and vomiting with onset of symptoms one day ago. His personal history was HIV+, diagnosed in 2013 and under regular treatment. On 5/25/22 resurfaced with the same symptoms of vertigo in conjunction with the appearance of an erythematous and painful vesicle in the right auricular region with edema and flushing of the region in association with PFP symptoms. On 05/30/22 he returned to the clinic with the same symptoms as before, and a magnetic resonance imaging of the temporal bones was done, showing an inflammatory process through the contrast at the bottom of the internal auditory canal suggestive of Bell's Palsy. (To see the complet abstract, please, check out the PDF.)

Herpes Zoster on a bladder cancer patient – a rare case

Introduction: Herpes zoster (HZ) is caused by reactivation of latent varicella-zoster virus (VZV) infection due to disturbance in T-cell mediated immunity. Risk factors include malignancy and therapy related to malignancy. Bladder cancer has a moderate association with HZ, with a risk increment of 10-50%. The rate of HZ in bladder cancer patients is 8/1000. Case description: A 57-years-old man with bladder cancer T4bN3M0 complained of a painful erythematous vesicular rash on the left front abdomen extended to the back 1 week prior, accompanied by fever and burning sensation. He has had regular chemotherapy using Gemcitabine and Cisplatin, and radiotherapy with 2 Gray doses each session. Dermatological examination showed multiple well-defined erythematous-based vesicles, clustered on the left abdominal, flank, and posterior thorax region at T7-T9 dermatome. Tzanck-smear examination showed multinucleated giant cells. The patient was given acyclovir, paracetamol, and wet dressing on vesicles. His chemoradiotherapy was also halted. On the 7th day of evaluation, there were no new lesions and his complaints improved. In cancer patients, CD4+ and CD8+ levels decreased, accompanied by lymphocyte proliferation impairment. Cytotoxic chemotherapy agents work by attacking proliferation cells, affecting immune-related cells. Ion radiation in radiotherapy interferes with a regional cellular immune response that inhibits viral reactivation. Conclusion: Principal HZ management in cancer patients includes antiviral and analgesics. In cancer patients, the occurrence of HZ can disturb and postpone management related to malignancy. The postponement of chemoradiotherapy is based on the patient's conditions and the severity of the disease.

Immunogenicity of Varicella Zoster Virus DNA Vaccines Encoding Glycoprotein E and Immediate Early Protein 63 in Mice.

Herpes zoster (HZ) is caused by the reactivation of latent varicella-zoster virus (VZV) from the sensory ganglia due to aging or immunosuppression. Glycoprotein E (gE) is a widely used vaccine antigen for specific humoral and cellular immune responses. Immediate early protein 63 (IE63) is expressed during latency, suggesting that it is a potential antigen against HZ reactivation. In this study, HZ DNA vaccines encoding gE, IE63, IE63-2A-gE (where 2A is a self-cleaving sequence), or IE63-linker-gE were developed and investigated for immunogenicity in mice. The results showed that each HZ DNA vaccine induced VZV-specific antibody production. The neutralizing antibody titer elicited by IE63-2A-gE was comparable to that elicited by gE or live attenuated HZ vaccine (LAV). IE63-2A-gE-induced gE or IE63-specific INF-γ+ T cell frequencies in splenocytes were comparable to those of LAV. Furthermore, IE63-2A-gE, gE, or IE63 led to a significant increase in IFN-γ (IE63 stimulation) and IL-2 (gE stimulation) secretion compared to LAV, showing a Th1-biased immune response. Moreover, IE63-2A-gE and gE induced cytotoxic activity of CD8+ T cells compared to that of LAV. This study elucidates that the IE63-2A-gE DNA vaccine can induce both humoral and cell-mediated immune responses, which provides a candidate for the development of an HZ vaccine.

An adjuvanted zoster vaccine elicits potent cellular immune responses in mice without QS21

Herpes zoster (HZ) is caused by reactivation of latent varicella-zoster virus (VZV) when VZV-specific cellular immunity is insufficient to control reactivation. Currently, Shingrix, which contains the VZV gE protein and GSK’s AS01B adjuvant composed of liposomes formulated with cholesterol, monophosphoryl lipid A (MPL) and QS21, is used for prevention of HZ. However, reactogenicity to Shingrix is common leading to poor patient compliance in receiving one or both shots. Here, we evaluated the immunogenicity of a newly formulated gE protein-based HZ vaccine containing Second-generation Lipid Adjuvant (SLA), a synthetic TLR4 ligand, formulated in an oil-in-water emulsion (SLA-SE) without QS21 (gE/SLA-SE). In VZV-primed mouse models, gE/SLA-SE-induced gE-specific humoral and cellular immune responses at comparable levels to those elicited by Shingrix in young mice, as both gE/SLA-SE and Shingrix induce polyfunctional CD4+ T-cell responses. In aged mice, gE/SLA-SE elicited more robust gE-specific T-cell responses than Shingrix. Furthermore, gE/SLA-SE-induced T-cell responses were sustained until 5 months after immunization. Thus, QS21-free, gE/SLA-SE is a promising candidate for development of gE-based HZ vaccines with high immunogenicity—particularly when targeting an older population.

The untapped potential of herpes zoster vaccination

Herpes zoster infection corresponds to the reactivation of latent varicella-zoster virus, and is characterised by a vesicular dermatomal rash, which usually spontaneously resolves, but can result in persistent (>3 months) debilitating pain, known as postherpetic neuralgia. Two vaccines are available against herpes zoster, namely zoster vaccine live (ZVL) and a newer, recombinant zoster vaccine (RZV), available since 2017.

Enhanced Potency and Persistence of Immunity to Varicella-Zoster Virus Glycoprotein E in Mice by Addition of a Novel BC02 Compound Adjuvant

Herpes zoster (HZ) is one of two distinct syndromes caused by Varicella-zoster virus (VZV). A primary infection with VZV causes varicella in susceptible young children. After resolution of the primary infection, VZV establishes a lifelong latency within the cranial or dorsal root ganglia. With increasing age, family history of shingles, immunosuppression or other risk factors, there is a decline in the virus-specific T-cell-mediated immune (CMI) response which allows reactivation of latent VZV in the root ganglia resulting in HZ. There are currently two vaccines that have been approved to prevent HZ and postherpetic neuralgia (PHN) but one is a live attenuated vaccine, the protective effect of which is considered to decrease significantly with the age of the recipient. However, a recombinant subunit vaccine may provide targeted VZV-specific cellular and humoral immunity, giving it a more potent and longer-lasting protective effect against HZ. The current study reports the development of a novel adjuvant, BC02 (BCG CpG DNA compound adjuvants system 02), composed of Al(OH)3 inorganic salt adjuvant and BC01 (BCG CpG DNA compound adjuvants system 01), a Toll-like receptor 9 (TLR9) agonist. Immunogenicity and compatibility with recombinant VZV glycoprotein E (gE) in mice were studied. The BC02-adjuvanted gE experimental vaccine was highly effective in eliciting both humoral and cellular immune responses to the recombinant gE glycoprotein and VZV-Oka in a mouse model. The efficient production and long-term persistence of gE and VZV-Oka-specific IFN-γ, IL-2-specific T cells and memory B cells in the early (1W), middle (7W), middle-late (15W), and final (27W) immune stages were established. Results of fluorescent antibody to membrane antigen (FAMA) and serum antibody plaque reduction tests also showed that the BC02 adjuvanted-gE experimental vaccine induced mice to secrete neutralizing antibodies against clinically isolated VZV strains. In combination, the current data suggest that the BC02 compound adjuvant offers a strategy to induce an appropriately strong cellular and humoral immunity against the VZV gE protein subunit to improve vaccine efficacy.

Case Report of Herpes Zoster in the 17-year-old Boy

Herpes zoster has been caused because of the reactivation of latent Varicella-Zoster virus. It is a proportionally uncommon condition in the young population, as compared with adults. After taking consent from the legal guardian of the patient, we report a 17-year-old boy with a history of varicella, who came to us with the complaint of very severe painful vesicular lesions on the right side T1 and T2 dermatomal distribution of the chest, arm, and dorsal side of the trunk. Ultimately, the patient was diagnosed with herpes zoster. We focus to highlight that herpes zoster could occur in the healthy and immunocompetent young population and this may be due to the previous subclinical infection or vaccine strain reactivation.

The adjuvanted recombinant zoster vaccine co-administered with the 13-valent pneumococcal conjugate vaccine in adults aged ≥50 years: A randomized trial

BackgroundHerpes zoster (HZ) results from reactivation of latent varicella-zoster virus. Adults at increased risk of HZ (due to immunocompromising conditions or older age) are also at risk of pneumococcal disease, both of which are preventable by vaccination. We evaluated simultaneous versus sequential administration of the adjuvanted recombinant zoster vaccine (RZV) and the 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥50 years. MethodsIn this phase IIIB multinational trial (NCT03439657), participants were randomized 1:1 to receive either the first RZV dose and PCV13 simultaneously followed by the second RZV dose two months later (Co-Ad, N = 449), or at two-month intervals, PCV13, the first RZV dose, and the second RZV dose sequentially (Control, N = 463). Objectives were to demonstrate that immune responses to both vaccines are non-inferior when co-administered compared to sequential administration and to evaluate the safety of their co-administration. ResultsThe RZV vaccine response rate (VRR) in the Co-Ad group was 99.1% (95% confidence interval [CI]: 97.6–99.7), meeting the VRR success criterion. Non-inferiority criteria for the Co-Ad versus Control group were also met for anti-glycoprotein E antibodies (adjusted geometric mean concentration Control/Co-Ad ratio 1.07 [95%CI: 0.99–1.16]) and all PCV13 serotypes (adjusted antibody geometric mean titer Control/Co-Ad ratios 1.02 [95%CI: 0.86–1.22] to 1.36 [95%CI: 1.07–1.73]). Upon co-administration, the frequency of solicited local adverse events was consistent with the known safety profile of each individual vaccine, whereas solicited general adverse events were within the same range as for RZV alone. ConclusionsRZV co-administered with PCV13 had an acceptable safety profile. Humoral immune responses to both vaccines were non-inferior when co-administered compared to sequential administration. These results suggest that adults may benefit from receiving RZV and a PCV at the same healthcare visit.

Ramsay Hunt Syndrome in a Patient with Ulcerative Colitis Treated with Infliximab.

Ramsay Hunt syndrome is a rare complication of herpes zoster that results from reactivation of varicella-zoster virus in the geniculate ganglion of the VII cranial nerve. Immunosuppression can lead to reactivation of latent varicella-zoster virus, resulting in herpes zoster. Here, we present a case of Ramsay Hunt syndrome in a patient with ulcerative colitis under treatment with infliximab.LEARNING POINTSRamsay Hunt syndrome is a rare form of herpes zoster and characterized by the presence of otalgia, facial palsy, vertigo and vesicular rash in the external ear or on the oropharynx.Treatment with TNF inhibitors increases the risk of its development.Although not generally recommended, vaccination may reduce the risk of herpes zoster recurrence during TNF inhibitor therapy.

Mutagenesis of the Varicella-Zoster Virus Genome Demonstrates That VLT and VLT-ORF63 Proteins Are Dispensable for Lytic Infection.

Primary varicella-zoster virus (VZV) infection leads to varicella and the establishment of lifelong latency in sensory ganglion neurons. Reactivation of latent VZV causes herpes zoster, which is frequently associated with chronic pain. Latent viral gene expression is restricted to the VZV latency-associated transcript (VLT) and VLT-ORF63 (VLT63) fusion transcripts. Since VLT and VLT63 encode proteins that are expressed during lytic infection, we investigated whether pVLT and pVLT-ORF63 are essential for VZV replication by performing VZV genome mutagenesis using CRISPR/Cas9 and BAC technologies. We first established that CRISPR/Cas9 can efficiently mutate VZV genomes in lytically VZV-infected cells through targeting non-essential genes ORF8 and ORF11 and subsequently show recovery of viable mutant viruses. By contrast, the VLT region was markedly resistant to CRISPR/Cas9 editing. Whereas most mutants expressed wild-type or N-terminally altered versions of pVLT and pVLT-ORF63, only a minority of the resulting mutant viruses lacked pVLT and pVLT-ORF63 coding potential. Growth curve analysis showed that pVLT/pVLT-ORF63 negative viruses were viable, but impaired in growth in epithelial cells. We confirmed this phenotype independently using BAC-derived pVLT/pVLT-ORF63 negative and repaired viruses. Collectively, these data demonstrate that pVLT and/or pVLT-ORF63 are dispensable for lytic VZV replication but promote efficient VZV infection in epithelial cells.

Herpes Zoster in a Patient With Ulcerative Colitis After Vedolizumab Initiation-Causal Link or Only Temporal Coincidence?

To the Editors, Herpes zoster results from the reactivation of latent varicella-zoster virus (VZV) in the cranial nerve or the dorsal root ganglia, with a higher rate in older persons or immunocompromised patients. Here, we report a case of herpes zoster eruption following the first dose of vedolizumab infusions in a 47-year-old man diagnosed with ulcerative colitis (UC). Previously, sulfasalazine and mesalazine failed to control UC activity in this patient. Given that no contraindications were found, vedolizumab was commenced in June 2021, with the patient also on mesalazine. Until this point, he had no previous episodes of herpes zoster eruption. However, 4 days after the first administration of vedolizumab, the patient developed a sore throat. On day 9 following the apparition of symptoms, scattered lesions on the right scapular area, right forearm, and fingers appeared, characterized by closely grouped papules and vesicles (Figure 1). The rash was preceded...