Molluscum contagiosum virus protein MC089 inhibits interferon regulatory factor 3 activation.

Molluscum contagiosum virus (MCV) is a human-specific poxvirus that causes a highly common but mild infection characterized by distinctive and persistent papular skin lesions. These lesions can persist for long periods without an effective clearance response from the host. MCV, like all poxviruses, encodes multiple known immunosuppressive proteins which target innate immune signalling pathways involved in viral nucleic acid sensing, interferon production and inflammation which should trigger antiviral immunity leading to clearance. Two major families of transcription factors responsible for driving the immune response to viruses are the NF-κB and the interferon regulatory factor (IRF) families. While NF-κB broadly drives pro-inflammatory gene expression and IRFs chiefly drive interferon induction, both collaborate in transactivating many of the same genes in a concerted immune response to viral infection. Here, we report that the MCV protein MC089 specifically inhibits IRF activation from both DNA- and RNA-sensing pathways, making it the first characterized MCV inhibitor to selectively target IRF activation to date. MC089 interacts with proteins required for IRF activation, namely IKKε, TBKBP1 and NAP1. Additionally, MC089 targets RNA sensing by associating with the RNA-sensing adaptor protein mitochondrial antiviral-signalling protein on mitochondria. MC089 displays specificity in its inhibition of IRF3 activation by suppressing immunostimulatory nucleic acid-induced serine 396 phosphorylation without affecting the phosphorylation of serine 386. The selective interaction of MC089 with IRF-regulatory proteins and site-specific inhibition of IRF3 phosphorylation may offer a tool to provide novel insights into the biology of IRF3 regulation.

Differential diagnosis of exanthematous viruses during the 2022 Mpox outbreak in Minas Gerais, Brazil.

The monkeypox virus (MPXV) outbreak, primarily endemic to Africa, has spread globally, with Brazil reporting the second-highest number of cases. The emergence of MPXV in non-endemic areas has raised concerns, particularly due to the co-circulation of other exanthematous viruses such as varicella-zoster virus (VZV) and molluscum contagiosum virus (MOCV). To perform an accurate differential diagnosis of MPXV during the ongoing outbreak in Minas Gerais, Brazil, a 5PLEX qPCR assay targeting orthopoxviruses (OPV), VZV, and MOCV was used to retrospectively analyze all clinical samples that tested negative for MPXV in the initial screening conducted at Funed. In summary, our study analyzed 1,175 clinical samples received from patients suspected of MPXV infection and found a positivity rate of 33.8% (397 samples) for MPXV using the non-variola qPCR assay. Testing the 778 MPXV-negative clinical samples using the 5PLEX qPCR assay revealed that 174 clinical samples (22.36%) tested positive for VZV. MOCV DNA was detected in 13 and other OPV in 3 clinical samples. The sequencing of randomly selected amplified clinical samples confirmed the initial molecular diagnosis. Analysis of patient profiles revealed a significant difference in the median age between groups testing positive for MPXV and VZV and a male predominance in MPXV cases. The geographic distribution of positive cases was concentrated in the most populous mesoregions of Minas Gerais state. This study highlights the challenges posed by emerging infectious diseases. It emphasizes the importance of epidemiological surveillance and accurate diagnosis in enabling timely responses for public health policies and appropriate medical care. IMPORTANCE: Brazil ranks second in the number of cases during the global monkeypox epidemic. The study, conducted in Minas Gerais, the second most populous state in Brazil with over 20 million inhabitants, utilized differential diagnostics, revealing a significant number of positive cases for other exanthematous viruses and emphasizing the need for accurate diagnoses. During the study, we were able to assess the co-circulation of other viruses alongside monkeypox, including varicella-zoster virus, molluscum contagiosum virus, and other orthopoxviruses. The significance of the research is underscored by the concentration of positive cases in populous areas, highlighting the challenges posed by emerging infectious diseases. This demographic context further amplifies the importance of the research in guiding public health policies and medical interventions, given the substantial population at risk. The study not only addresses a global concern but also holds critical implications for a state with such a large population and geographic expanse within Brazil. Overall, the study emphasizes the pivotal role of surveillance and precise diagnosis in guiding effective public health responses and ensuring appropriate medical interventions.

Molluscum Contagiosum Virus Protein MC008 Targets NF-κB Activation by Inhibiting Ubiquitination of NEMO.

Molluscum contagiosum virus (MCV) is a human-adapted poxvirus that causes a common and persistent yet mild infection characterized by distinct, contagious, papular skin lesions. These lesions are notable for having little or no inflammation associated with them and can persist for long periods without an effective clearance response from the host. Like all poxviruses, MCV encodes potent immunosuppressive proteins that perturb innate immune pathways involved in virus sensing, the interferon response, and inflammation, which collectively orchestrate antiviral immunity and clearance, with several of these pathways converging at common signaling nodes. One such node is the regulator of canonical nuclear factor kappa B (NF-κB) activation, NF-κB essential modulator (NEMO). Here, we report that the MCV protein MC008 specifically inhibits NF-κB through its interaction with NEMO, disrupting its early ubiquitin-mediated activation and subsequent downstream signaling. MC008 is the third NEMO-targeting inhibitor to be described in MCV to date, with each inhibiting NEMO activation in distinct ways, highlighting strong selective pressure to evolve multiple ways of disabling this key signaling protein. IMPORTANCE Inflammation lies at the heart of most human diseases. Understanding the pathways that drive this response is the key to new anti-inflammatory therapies. Viruses evolve to target inflammation; thus, understanding how they do this reveals how inflammation is controlled and, potentially, how to disable it when it drives disease. Molluscum contagiosum virus (MCV) has specifically evolved to infect humans and displays an unprecedented ability to suppress inflammation in our tissue. We have identified a novel inhibitor of human innate signaling from MCV, MC008, which targets NEMO, a core regulator of proinflammatory signaling. Furthermore, MC008 appears to inhibit early ubiquitination, thus interrupting later events in NEMO activation, thereby validating current models of IκB kinase (IKK) complex regulation.

Systematic review of the evidence for treatment and management of common skin conditions in resource-limited settings: An update.

INTRODUCTION: The skin is the largest and most visible organ of the human body. As such, skin infections can have a significant impact on overall health, social wellbeing and self-image. In 2019, we published a systematic review of the treatment, prevention and public health control of skin infections including impetigo, scabies, crusted scabies and tinea in resource-limited settings where skin infections are endemic. This current review serves as an update to assess the evidence for treatment of these conditions as well as atopic dermatitis, molluscum contagiosum and head lice in endemic settings. The data from this systematic review have supported an update to the Australian National Healthy Skin guidelines. METHODS: A systematic review was conducted using two separate searches in MEDLINE, PubMed, Embase, CINAHL, Cochrane and Web of Science. The first search was an update of the 2018 systematic review using the same search strategy for the same skin conditions to identify emerging literature from 2018 to 2022. The second search strategy used the same key terms but with the addition of atopic dermatitis, head lice and molluscum contagiosum from 1960 to 2022. Eligible studies included Indigenous peoples and populations in resource-limited settings with a diagnosis of impetigo, scabies, crusted scabies, tinea capitis, atopic dermatitis, molluscum contagiosum or who presented with head lice. Studies conducted in high-income countries were excluded. Articles were screened for inclusion independently by one author with a second group of reviewers independently double screening. Data extraction and an in-depth quality assessment conducted by one author and checked by two others. RESULTS: Of 1466 original articles identified, 68 studies were included and key findings outlined for impetigo, scabies, crusted scabies, atopic dermatitis, head lice and molluscum contagiosum. Recommendations for each condition based on the available evidence are provided. CONCLUSION: The importance of assessing literature relevant to the populations with heavy burden of skin infections is outlined in this systematic review. We have summarised updates to this literature, which may benefit in developing guidelines for skin infection management similar to the National Healthy Skin Guidelines for Australia.

Berdazimer gel for molluscum contagiosum: An integrated analysis of 3 randomized controlled trials.

BACKGROUND: An out-of-office therapeutic agent indicated for molluscum contagiosum is needed. OBJECTIVE: To assess the efficacy and safety of berdazimer gel, 10.3% (a topical, antiviral, nitric oxide-releasing medication) versus vehicle. METHODS: Berdazimer gel, 10.3% or vehicle was applied once daily to all molluscum contagiosum lesions for 12 weeks in patients ≥6 months with 3-70 mollusca. Efficacy assessment: complete lesion clearance and partial clearance at week 12. Safety and tolerability assessment: adverse events through week 24 and local skin reactions through week 12. RESULTS: There were 1598 patients enrolled (n = 917 berdazimer, n = 681 vehicle). Berdazimer was superior to vehicle at week 12 in complete clearance rates, 30.0% versus 19.8% (odds ratio, 1.75; 95% CI, 1.38-2.23, P < .001). Subgroup analyses of primary efficacy showed consistent favorable efficacy for berdazimer across most subgroups, including age, sex, baseline lesion count, and disease duration. Berdazimer provided favorable outcome for partial clearance. Application-site pain (18.7% vs 4.8% in berdazimer vs vehicle) and erythema (11.7% vs 1.3%), mostly mild to moderate, were the most common local skin reactions. LIMITATIONS: Berdazimer sodium in molluscum patients with lesions (B-SIMPLE) trials enrolled only US patients; no efficacy assessments beyond week 12. CONCLUSIONS: Berdazimer gel, 10.3% showed favorable efficacy and safety across subgroups.

Poxviruses in Children.

The family Poxviridae is a large family of viruses with a ubiquitous distribution, subdivided into two subfamilies: Chordopoxvirinae (poxviruses of vertebrates) and Entomopoxvirinae (poxviruses of insects). Only three species from the first subfamily, Orthopoxvirus (OPV), Molluscipoxvirus and Parapoxvirus, can infect the human being. In the paediatric population, viruses belonging to the first two subfamilies have the greatest importance. Following the eradication of smallpox in 1980, vaccination of the general population was discontinued after careful consideration of the risks and benefits. However, nearly all children and most of the world's population had little to no protection against OPV. The aim of this chapter is to review the current evidence on the aetiology, clinical manifestations, diagnosis and management of Poxviridae infections in children.

Molluscum Contagiosum Virus: Biology and Immune Response.

Molluscum contagiosum virus is a poxvirus belonging to the Poxviridae family, which includes Orthopoxvirus, Parapoxvirus, Yantapoxvirus, Molluscipoxvirus, Smallpox virus, Cowpox virus and Monkeypox virus. MCV belongs to the genus Molluscipoxvirus and has a tropism for skin tissue. MCV infects keratinocytes and, after an incubation period of 2 weeks to 6 weeks, causes a breakdown of the skin barrier with the development of papules of variable size depending on the proper functioning of the immune response (both adaptive and acquired). MCV only infects humans and does not cause viraemia. MCV encodes for several inhibitory proteins responsible to circumvent the immune response through different signalling pathways. Individuals who can be infected with MCV are children, immunocompromised individuals such as organ transplant recipients and Human Immunodeficiency Virus (HIV)-infected individuals. Current treatments to manage MCV-induced lesions are different and include the use of immunomodulators, which, however, do not provide an effective response.

Berdazimer gel for molluscum contagiosum in patients with atopic dermatitis.

OBJECTIVE: Controlling molluscum contagiosum (MC) infections is critical in atopic dermatitis (AD) management. This post hoc analysis assessed the efficacy and safety of berdazimer gel, 10.3% (topical, antiviral, nitric oxide-releasing medication) versus vehicle in MC patients with or without AD. METHODS: Three Phase 3, multicenter, randomized, double-blind, vehicle-controlled, parallel-group trials (B-SIMPLE[berdazimer sodium in molluscum patients with lesions]1, -2, -4) enrolled patients 6 months and older with 3-70 mollusca. Berdazimer or vehicle was applied once daily to all MC lesions for 12 weeks. Data from three Phase 3 studies were integrated for subgroup efficacy and safety assessments using several weighted meta-analysis approaches. Patients with concurrent AD or a history of AD/eczema were categorized as AD+ subgroup (AD- when absent). Primary efficacy endpoint: complete lesion clearance at Week 12. Safety endpoints included adverse events (AEs) through Week 24 and local skin reactions through Week 12. RESULTS: Of 1598 enrolled patients, 209 (13.1%) were AD+. Baseline mean lesion counts were greater in AD+ (26.4) than AD- (19.3). Complete clearance rates were higher at Week 12 for berdazimer compared with vehicle in AD+ (n = 209; 35.0% vs. 27.4%; odds ratio [OR], 1.3; 95% CI, 0.7-2.5) and AD- (n = 1389; 29.1% vs. 18.9%; OR 1.8; 95% CI 1.4-2.4) subgroups. AEs in AD+ were application-site pain (21.6% with berdazimer vs. 11.9% with vehicle), dermatitis (12.8% vs. 2.4%), and erythema (9.6% vs. 7.1%). CONCLUSIONS: Berdazimer gel showed favorable efficacy regardless of AD status. Berdazimer-induced erythema may be indistinguishable from AD symptoms or with inflammatory response upon resolution of molluscum.

Clinical, immunological and molecular findings of patients with DOCK-8 deficiency from India.

DOCK8 deficiency affects various cell subsets belonging to both the innate and adaptive immune systems. Clinical diagnosis is challenging, as many cases present with severe atopic dermatitis as the only initial manifestation. Though flow cytometry helps in the presumptive diagnosis of DOCK8-deficient patients by evaluating their DOCK8 protein expression, it requires subsequent confirmation by molecular genetic analysis. Currently, haematopoietic stem cell transplantation (HSCT) is the only curative treatment option available for these patients. There is a paucity of data from India on the clinical diversity and molecular spectrum of DOCK8 deficiency. In the present study, we report the clinical, immunological and molecular findings of 17 DOCK8-deficient patients from India diagnosed over the last 5 years.

The MC160 protein of the molluscum contagiosum virus dampens cGAS/STING-induced interferon-ß activation.

Molluscum contagiosum virus (MCV) is a poxvirus that causes benign, persistent skin lesions. MCV encodes a variety of immune evasion molecules to dampen host immune responses. Two of these proteins are the MC159 and MC160 proteins. Both MC159 and MC160 contain two tandem death effector domains and share homology to the cellular FLIPs, FADD, and procaspase-8. MC159 and MC160 dampen several innate immune responses such as NF-κB activation and mitochondrial antiviral signaling (MAVS)-mediated induction of type 1 interferon (IFN). The type 1 IFN response is also activated by the cytosolic DNA sensors cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). Both cGAS and STING play a vital role in sensing a poxvirus infection. In this study, we demonstrate that there are nuanced differences between both MC160 and MC159 in terms of how the viral proteins modulate the cGAS/STING and MAVS pathways. Specifically, MC160 expression, but not MC159 expression, dampens cGAS/STING-mediated induction of IFN in HEK 293 T cells. Further, MC160 expression prevented the K63-ubiquitination of both STING and TBK1, a kinase downstream of cGAS/STING. Ectopic expression of the MC160 protein, but not the MC159 protein, resulted in a measurable decrease in the TBK1 protein levels as detected via immunoblotting. Finally, using a panel of MC160 truncation mutants, we report that the MC160 protein requires both DEDs to inhibit cGAS/STING-induced activation of IFN-ß. Our model indicates MC160 likely alters the TBK1 signaling complex to decrease IFN-ß activation at the molecular intersection of the cGAS/STING and MAVS signaling pathways.

Heterologous effect of influenza vaccination on molluscum contagiosum infection; a case report of siblings.

BACKGROUND: Molluscum contagiosum virus (MCV) is a benign, common cutaneous infection predominantly affecting the younger pediatric population. Traditional treatments may be time consuming with variable efficacy. Time to spontaneous resolution is variable and treatment is often sought to shorten duration of infection, prevent further autoinoculation, prevent infectious spread to others and treat cosmetic intolerability. CASE PRESENTATION: We present the case of two patients with complete, simultaneous clearance of their molluscum contagiosum infections after receiving a routine 2018 quadrivalent influenza vaccination. Neither patient has had recurrence of molluscum contagiosum or permanent scarring. We review trials of intralesional immunotherapy in treatment of cutaneous infections to theorize the mechanism of MCV infection clearance post influenza vaccination. CONCLUSION: We propose a delayed-type hypersensitivity reaction was induced as a heterologous effect of the influenza vaccination, similar to that seen in current immunotherapy treatments. This is the first reported case of MCV-directed immune reaction with infection clearance after influenza vaccination.

Safety and efficacy of topical nitric oxide-releasing berdazimer gel for molluscum contagiosum clearance: A systematic review and meta-analysis of randomized controlled trials.

Molluscum contagiosum (MC) is a contagious infection that, although benign, can become an aesthetic burden and lead to other opportunistic infections, secondary dermatitis, and self-isolation. Currently, several treatment options are available for MC, including the newly investigated nitric oxide-releasing berdazimer gel, leading this review to evaluate randomized controlled trials (RCT) comparing berdazimer gel with a vehicle for treating MC. The meta-analysis included three reports and four RCT involving 1854 patients, with 1106 (59.6%) randomized to receive berdazimer. Our findings suggest that berdazimer is effective in the management of MC lesions, but the increased clearance of lesions and reduction of scarring must be weighed against the potential for topical adverse effects, particularly when considering the use of this therapy in pediatric patients.

Comparative efficacy of treatments for molluscum contagiosum: A systematic review and network meta-analysis.

BACKGROUND AND OBJECTIVES: Various interventions have been applied to treat molluscum contagiosum, but benefits and efficacy remain unclear. To assess the comparative efficacy and safety of interventions for molluscum contagiosum, a network meta-analysis was performed. PATIENTS AND METHODS: Embase, PubMed, and the Cochrane Library were searched for articles published between January 1, 1990, and November 31, 2020. Eligible studies were randomized clinical trials (RCTs) of interventions in immunocompetent children and adults with genital/non-genital molluscum contagiosum lesions. RESULTS: Twelve interventions from 25 RCTs including 2,123 participants were assessed. Compared with the placebo, ingenol mebutate had the most significant effect on complete clearance (odds ratio [OR] 117.42, 95% confidence interval [CI] 6.37-2164.88), followed by cryotherapy (OR 16.81, 95% CI 4.13-68.54), podophyllotoxin (OR 10.24, 95% CI 3.36-31.21), and potassium hydroxide (KOH) (OR 10.02, 95% CI 4.64-21.64). Data on adverse effects were too scarce for quantitative synthesis. CONCLUSIONS: Ingenol mebutate, cryotherapy, podophyllotoxin, and KOH were more effective than the other interventions in achieving complete clearance, but safety concerns regarding ingenol mebutate have recently been reported. Due to the possibility of spontaneous resolution, observation is also justified for asymptomatic infection. Factors including adverse effects, cost, patient preference, and medical accessibility should be considered.

Molluscum contagiosum of the corneal limbus in an AIDS patient: a clinicopathological case report.

BACKGROUND: Molluscum contagiosum, a pox virus infection, is likely to occur in the eyelid skin; however, corneal involvements by molluscum lesions are extremely rare. We report a case of molluscum contagiosum arising in the corneal limbus in an untreated AIDS patient, together with anterior segment optical coherence tomography (OCT) findings and histopathology of the excised tumor. CASE PRESENTATION: A 46-year-old man with AIDS was referred to our department for the management of an ocular lesion. Blood tests revealed an extremely low CD4+ T-cell count of 11 cells/µL, being strongly positive for anti-HIV antibody (591.36 S/CO) with a high copy number of HIV RNA (8070.0 × 100 copy/mL). Slit-lamp examination of his right eye showed a white nodule at the lower limbus. Anterior segment OCT findings of the nodule revealed a highly reflective elevated lesion, which was considered to involve the Bowman layer. The nodular lesion was excised from the limbus including the superficial corneal stroma, and then processed for histologic examination. Histopathology of the excised lesion showed acanthotic corneal epithelium containing swollen cells with eosinophilic inclusions known as molluscum bodies. He was diagnosed with molluscum contagiosum. CONCLUSIONS: Anterior segment OCT findings provide useful information for morphological evaluations of and preoperative strategies against molluscum contagiosum.

In vivo evaluation of facial papule dermatoses with reflectance confocal microscopy in children.

BACKGROUND: Molluscum contagiosum (MC), milia, keratosis pilaris (KP), verruca plana (VP), seborrheic keratosis (SK), and juvenile xanthogranuloma (JXG) are common papule dermatoses on the face of children that have a similar appearance. In vivo evaluation of facial papule dermatoses with reflectance confocal microscopy (RCM) is helpful in the diagnosis of these ambiguous lesions in children. The purpose of this study was to clarify the RCM characteristics of MC, milia, KP, VP, SK, and JXG and explore the clinical application value of RCM for these common facial papule dermatoses. METHODS: We recruited 113 patients referred for unequivocal facial papule dermatosis, including 21 patients with MC, 17 patients with milia, 19 patients with KP, 36 patients with VP, 8 patients with SK, and 12 patients with JXG. We evaluated the characteristics and distinguishing features of the six kinds of facial papule dermatoses using RCM. RESULTS: The main RCM features of the six dermatoses included a well-demarcated border of the lesion area. MC, milia and KP all manifested cyst-like structures, and their distinguishing features were the location of the cystic structures and the refractive index of the contents. Although VP, SK, and JXG did not have obvious cystoid structures, VP was typically characterized by uniformly distributed petal-like structures with a medium-to-high refractive index in the epidermis. With regard to SK, the characteristic features were an obviously thickened epidermis and cobblestone-like structures. JXG was mainly characterized by multiple large round and ovoid cells with a foamy cytoplasm, and discoid-shaped multinucleated large cells were diffusely distributed in the dermis. CONCLUSION: RCM allows the real-time visualization of major key diagnostic and distinguishing features of common facial papule dermatoses in children, including MC, milia, KP, VP, SK, and JXG.

[Infectious genital lesions]. / Lésions infectieuses génitales.

External genital infections are multiple, possibly linked to viral, bacterial, mycosic, or parasitic infections. Viral and bacterial infections often integrate within the framework of Sexually Transmitted Diseases (STD/STI) and can be associated with a context of immunosuppression. Skin or mucosae damage is often isolated. Their diagnosis is often referred to clinically, and confirmed by local samples without the need for biopsy. Histological examination is indicated in unusual clinical cases or in cases of persistent lesions or atypical appearance or pseudotumoral, posing a challenge for clinical differential diagnosis. In these cases, the morphological analysis can be supplemented by special colorations, immunological techniques or even molecular analysis allowing in some cases the detection and identification of infectious agents. This chapter will integrate external genital infections of viral, bacterial and parasitic origin where histological analysis is the diagnostic element of orientation.

Demographic and clinic characteristics and risk factors of molluscum contagiosum in children.

OBJECTIVE: To address the gap in evidence related to molluscum contagiosum in children by focusing on demographic and clinical features as well as risk factors. Methods: The multicentre, prospective, clinical study was conducted at four hospitals in Ankara and Tokat cities of Turkey from August 1, 2014, to August 5, 2019, and comprised patients aged ≤18 years diagnosed with molluscum contagiosum. Data about demographics, day nursery and preschool attendance, the seasons when the disease occurred, any use of Turkish baths and swimming pools, history of personal/familial atopy, coexistence of diseases, disease duration, courses, number of lesions and anatomic localisation. Data was analysed using SPSS 19. RESULTS: Of the 286 patients, 130(45.5%) were girls and 156(54.5%) were boys. The overall mean age was 5.94±3.95 years. The median duration of the disease was 5 weeks (interquartile range: 3.00-12.00 weeks). There was a significant number of cases with family history 18(48.6%) in the 0-3 age group (p=0.027). History of personal atopy was significantly high in the winter season (p<0.05). Patients with >20 lesions had used swimming pools significantly more frequently than the rest (p=0.042). The trunk was the most commonly involved region 162(56.6%). CONCLUSIONS: Providing prospective data about demographics, clinical characteristics and risk factors of molluscum contagiosum in children will lead to appropriate preventive and therapeutic measures.

Viral Infections Confined to Tattoos-A Narrative Review.

Since ancient times, people have tattooed their skin for various reasons. In the past, tattoos were associated with low social status; nowadays, tattoos are very popular and are considered a form of art. However, tattoos are associated with various clinical problems, including immune reactions, inflammatory disorders, infections, and even skin cancer. Epidemiological and clinical data of infections on tattoos are scarce. Tattoo-related infections are mostly bacterial; only a few localized viral infections have been reported so far and are caused by molluscum contagiosum virus (MCV), human papillomavirus (HPV), and herpes simplex virus (HSV). In most cases, the lesions were strictly confined to the area of the tattoo. In this review, we have analysed reported cases of viral infections localized on tattoos and discussed the possible mechanisms involved in the occurrence of these infections.

The Molluscum Contagiosum Gene MC021L Partially Compensates for the Loss of Its Vaccinia Virus Homolog, F13L.

Orthopoxviruses produce two antigenically distinct infectious enveloped virions termed intracellular mature virions and extracellular virions (EV). EV have an additional membrane compared to intracellular mature virions due to a wrapping process at the trans-Golgi network and are required for cell-to-cell spread and pathogenesis. Specific to the EV membrane are a number of proteins highly conserved among orthopoxviruses, including F13, which is required for the efficient wrapping of intracellular mature virions to produce EV and which plays a role in EV entry. The distantly related molluscipoxvirus, molluscum contagiosum virus, is predicted to encode several vaccinia virus homologs of EV-specific proteins, including the homolog of F13L, MC021L. To study the function of MC021, we replaced the F13L open reading frame in vaccinia virus with an epitope-tagged version of MC021L. The resulting virus (vMC021L-HA) had a small-plaque phenotype compared to vF13L-HA but larger than vΔF13L. The localization of MC021-HA was markedly different from that of F13-HA in infected cells, but MC021-HA was still incorporated in the EV membrane. Similar to F13-HA, MC021-HA was capable of interacting with both A33 and B5. Although MC021-HA expression did not fully restore plaque size, vMC021L-HA produced amounts of EV similar to those produced by vF13L-HA, suggesting that MC021 retained some of the functionality of F13. Further analysis revealed that EV produced from vMC021L-HA exhibit a marked reduction in target cell binding and an increase in dissolution, both of which correlated with a small-plaque phenotype.IMPORTANCE The vaccinia virus extracellular virion protein F13 is required for the production and release of infectious extracellular virus, which in turn is essential for the subsequent spread and pathogenesis of orthopoxviruses. Molluscum contagiosum virus infects millions of people worldwide each year, but it is unknown whether EV are produced during infection for spread. Molluscum contagiosum virus contains a homolog of F13L termed MC021L. To study the potential function of this homolog during infection, we utilized vaccinia virus as a surrogate and showed that a vaccinia virus expressing MC021L-HA in place of F13L-HA exhibits a small-plaque phenotype but produces similar levels of EV. These results suggest that MC021-HA can compensate for the loss of F13-HA by facilitating wrapping to produce EV and further delineates the dual role of F13 during infection.

Intralesional measles, mumps, and rubella vaccine immunotherapy in molluscum contagiosum: A retrospective observational study from a tertiary care center in north India.

Molluscum contagiosum (MC) is a mucocutaneous viral infection, often self-limiting but untreated lesions can often last for 2 months to 2 years. Previously intralesional measles, mumps, and rubella (MMR) vaccine has been tried for the treatment of warts but no studies exist of its use in MC. We report our experience with intralesional MMR in 22 patients of MC. The study was carried out to assess the efficacy and safety of intralesional MMR vaccine in patients of MC. We retrospectively analyzed records of patients who received intralesional MMR for MC from September 2018 to September 2019. Demographic characteristics, number, size, and site of molluscum lesions, number of MMR injections given, and response were recorded. Records of 22 patients were analyzed. There were 10 males and 12 females. The age of the patients ranged from 6 to 50 years with a mean of 19.72 ± 10.92. At the end of 12 weeks, 18 patients (81.8%) had complete clearance of lesions, with 4 patients (18.18%) having a partial response of more than 50%. No patient showed less than 50% or no response. In only one patient who had giant molluscum, postinflammatory hyperpigmentation was noted. No other adverse effect was seen in any of the patients. MMR is a safe, effective, easy to administer, time-saving, and inexpensive therapy for lesions of MC.