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Acta Dermato-venereologica Aug 2018
Topics: Adolescent; Dermoscopy; Female; Humans; Molluscum Contagiosum; Molluscum contagiosum virus; Sacrococcygeal Region; Skin
PubMed: 29701237
DOI: 10.2340/00015555-2955 -
Human Genomics Feb 2024Periodic bioinformatics-based screening of wastewater for assessing the diversity of potential human viral pathogens circulating in a given community may help to...
BACKGROUND
Periodic bioinformatics-based screening of wastewater for assessing the diversity of potential human viral pathogens circulating in a given community may help to identify novel or potentially emerging infectious diseases. Any identified contigs related to novel or emerging viruses should be confirmed with targeted wastewater and clinical testing.
RESULTS
During the COVID-19 pandemic, untreated wastewater samples were collected for a 1-year period from the Great Lakes Water Authority Wastewater Treatment Facility in Detroit, MI, USA, and viral population diversity from both centralized interceptor sites and localized neighborhood sewersheds was investigated. Clinical cases of the diseases caused by human viruses were tabulated and compared with data from viral wastewater monitoring. In addition to Betacoronavirus, comparison using assembled contigs against a custom Swiss-Prot human virus database indicated the potential prevalence of other pathogenic virus genera, including: Orthopoxvirus, Rhadinovirus, Parapoxvirus, Varicellovirus, Hepatovirus, Simplexvirus, Bocaparvovirus, Molluscipoxvirus, Parechovirus, Roseolovirus, Lymphocryptovirus, Alphavirus, Spumavirus, Lentivirus, Deltaretrovirus, Enterovirus, Kobuvirus, Gammaretrovirus, Cardiovirus, Erythroparvovirus, Salivirus, Rubivirus, Orthohepevirus, Cytomegalovirus, Norovirus, and Mamastrovirus. Four nearly complete genomes were recovered from the Astrovirus, Enterovirus, Norovirus and Betapolyomavirus genera and viral species were identified.
CONCLUSIONS
The presented findings in wastewater samples are primarily at the genus level and can serve as a preliminary "screening" tool that may serve as indication to initiate further testing for the confirmation of the presence of species that may be associated with human disease. Integrating innovative environmental microbiology technologies like metagenomic sequencing with viral epidemiology offers a significant opportunity to improve the monitoring of, and predictive intelligence for, pathogenic viruses, using wastewater.
Topics: Humans; Wastewater; Michigan; Pandemics; Viruses; Enterovirus; Virus Diseases
PubMed: 38321488
DOI: 10.1186/s40246-024-00581-0 -
BMC Pediatrics May 2023Molluscum contagiosum virus (MCV) is a benign, common cutaneous infection predominantly affecting the younger pediatric population. Traditional treatments may be time... (Review)
Review
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.
Topics: Humans; Child; Molluscum Contagiosum; Siblings; Influenza, Human; Molluscum contagiosum virus; Immunotherapy
PubMed: 37127556
DOI: 10.1186/s12887-023-04019-9 -
Journal of Virology Sep 2020Orthopoxviruses produce two antigenically distinct infectious enveloped virions termed intracellular mature virions and extracellular virions (EV). EV have an additional...
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 -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. 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.
Topics: Cell Membrane; Genetic Complementation Test; HeLa Cells; Humans; Membrane Proteins; Molluscum contagiosum virus; Vaccinia virus; Viral Envelope Proteins; Virion
PubMed: 32727873
DOI: 10.1128/JVI.01496-20 -
Antiviral Research Mar 2023Molluscum contagiosum (MC) is an infectious disease that occurs only in humans with a tropism that is narrowly restricted to the outermost epidermal layer of the skin....
Molluscum contagiosum (MC) is an infectious disease that occurs only in humans with a tropism that is narrowly restricted to the outermost epidermal layer of the skin. Molluscum contagiosum virus (MCV) is the causative agent of MC which produces skin lesions that can persist for months to several years. MCV is efficiently transmitted by direct physical contact or by indirect contact with fomites. MC is most prevalent in children and immune compromised patients. The failure to develop a drug that targets MCV replication has been hampered for decades by the inability to propagate MCV in cell culture. To address this dilemma, we recently engineered a surrogate poxvirus expressing the MCV processivity factor (mD4) as the drug target. The mD4 protein is essential for viral replication by keeping the viral polymerase tethered to the DNA template. In this study we have designed and synthesized a lead compound (7269) that is able to prevent mD4 dependent processive DNA synthesis in vitro (IC = 6.8 μM) and effectively inhibit propagation of the mD4-VV surrogate virus in BSC-1 cells (EC = 13.2 μM) with negligible cytotoxicity. In human liver microsomes, 7269 was shown to be stable for almost 2 h. When tested for penetration into human cadaver skin in a formulated gel, the level of 7269 in the epidermal layer was nearly 100 times the concentration (EC) needed to inhibit propagation of the mD4-VV surrogate virus in BSC-1 cells. The gel formulated 7269 was scored as a non-irritant on skin and shown to have a shelf-life that was completely stable after several months. In summary, 7269 is a potential Lead for becoming the first MCV anti-viral compound to treat MC and thereby, addresses this unmet medical need that has persisted for many decades.
Topics: Child; Humans; Molluscum contagiosum virus; Viral Proteins; Molluscum Contagiosum; DNA
PubMed: 36603771
DOI: 10.1016/j.antiviral.2022.105520 -
Italian Journal of Dermatology and... Jun 2021
Topics: Adjuvants, Immunologic; Echinacea; Humans; Molluscum Contagiosum; Molluscum contagiosum virus; Recurrence
PubMed: 33016668
DOI: 10.23736/S2784-8671.20.06644-4 -
PLoS Pathogens Apr 2019The human specific poxvirus molluscum contagiosum virus (MCV) produces skin lesions that can persist with minimal inflammation, suggesting that the virus has developed...
The human specific poxvirus molluscum contagiosum virus (MCV) produces skin lesions that can persist with minimal inflammation, suggesting that the virus has developed robust immune evasion strategies. However, investigations into the underlying mechanisms of MCV pathogenesis have been hindered by the lack of a model system to propagate the virus. Herein we demonstrate that MCV-encoded MC80 can disrupt MHC-I antigen presentation in human and mouse cells. MC80 shares moderate sequence-similarity with MHC-I and we find that it associates with components of the peptide-loading complex. Expression of MC80 results in ER-retention of host MHC-I and thereby reduced cell surface presentation. MC80 accomplishes this by engaging tapasin via its luminal domain, targeting it for ubiquitination and ER-associated degradation in a process dependent on the MC80 transmembrane region and cytoplasmic tail. Tapasin degradation is accompanied by a loss of TAP, which limits MHC-I access to cytosolic peptides. Our findings reveal a unique mechanism by which MCV undermines adaptive immune surveillance.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 2; Animals; Antigen Presentation; Cells, Cultured; Endoplasmic Reticulum; Endoplasmic Reticulum-Associated Degradation; Histocompatibility Antigens Class I; Humans; Immune Evasion; Membrane Transport Proteins; Mice; Molluscum Contagiosum; Molluscum contagiosum virus; T-Lymphocytes, Cytotoxic; Viral Proteins
PubMed: 31034515
DOI: 10.1371/journal.ppat.1007711 -
Journal of Virology May 2016Molluscum contagiosum virus (MOCV), the only circulating human-specific poxvirus, has a worldwide distribution and causes benign skin lesions that may persist for months...
UNLABELLED
Molluscum contagiosum virus (MOCV), the only circulating human-specific poxvirus, has a worldwide distribution and causes benign skin lesions that may persist for months in young children and severe infections in immunosuppressed adults. Studies of MOCV are restricted by the lack of an efficient animal model or a cell culture replication system. We used next-generation sequencing to analyze and compare polyadenylated RNAs from abortive MOCV infections of several cell lines and a human skin lesion. Viral RNAs were detected for 14 days after MOCV infection of cultured cells; however, there was little change in the RNA species during this time and a similar pattern occurred in the presence of an inhibitor of protein synthesis, indicating a block preventing postreplicative gene expression. Moreover, a considerable number of MOCV RNAs mapped to homologs of orthopoxvirus early genes, but few did so to homologs of intermediate or late genes. The RNAs made during in vitro infections represent a subset of RNAs detected in human skin lesions which mapped to homologs of numerous postreplicative as well as early orthopoxvirus genes. Transfection experiments using fluorescent protein and luciferase reporters demonstrated that vaccinia virus recognized MOCV intermediate and late promoters, indicating similar gene regulation. The specific recognition of the intermediate promoter in MOCV-infected cells provided evidence for the synthesis of intermediate transcription factors, which are products of early genes, but not for late transcription factors. Transcriptome sequencing (RNA-seq) and reporter gene assays may be useful for testing engineered cell lines and conditions that ultimately could provide an in vitro replication system.
IMPORTANCE
The inability to propagate molluscum contagiosum virus, which causes benign skin lesions in young children and more extensive infections in immunosuppressed adults, has constrained our understanding of the biology of this human-specific virus. In the present study, we characterized the RNAs synthesized in abortively infected cultured cells and a human skin lesion by next-generation sequencing. These studies provided an initial transcription map of the MOCV genome, suggested temporal regulation of gene expression, and indicated that the in vitro replication block occurs prior to intermediate and late gene expression. RNA-seq and reporter assays, as described here, may help to further evaluate MOCV gene expression and define conditions that could enable MOCV replication in vitro.
Topics: Cell Line; Cells, Cultured; Computational Biology; Consensus Sequence; Gene Expression Profiling; Gene Expression Regulation, Viral; Gene Order; Genes, Viral; Genome, Viral; Humans; Molecular Sequence Annotation; Molluscum Contagiosum; Molluscum contagiosum virus; Promoter Regions, Genetic; RNA, Viral; Sequence Analysis, DNA; Transcriptome
PubMed: 26889040
DOI: 10.1128/JVI.02911-15 -
Journal of Virology May 2019MC159 is a viral FLIP (FLICE inhibitory protein) encoded by the molluscum contagiosum virus (MCV) enabling MCV to evade antiviral immunity and to establish persistent...
MC159 is a viral FLIP (FLICE inhibitory protein) encoded by the molluscum contagiosum virus (MCV) enabling MCV to evade antiviral immunity and to establish persistent infections in humans. Here, we show that MC159 contains a functional SH3 binding motif, which mediates avid and selective binding to SH3BP4, a signaling protein known to regulate endocytic trafficking and suppress cellular autophagy. The capacity to bind SH3BP4 was dispensable for regulation of NF-κB-mediated transcription and suppression of proapoptotic caspase activation but contributed to inhibition of amino acid starvation-induced autophagy by MC159. These results provide new insights into the cellular functions of MC159 and reveal SH3BP4 as a novel host cell factor targeted by a viral immune evasion protein. After the eradication of smallpox, molluscum contagiosum virus (MCV) is the only poxvirus restricted to infecting humans. MCV infection is common and causes benign skin lesions that usually resolve spontaneously but may persist for years and grow large, especially in immunocompromised individuals. While not life threatening, MCV infections pose a significant global health burden. No vaccine or specific anti-MCV therapy is available. MCV encodes several proteins that enable it to evade antiviral immunity, a notable example of which is the MC159 protein. In this study, we describe a novel mechanism of action for MC159 involving hijacking of a host cell protein called SH3BP4 to suppress autophagy, a cellular recycling mechanism important for antiviral immunity. This study contributes to our understanding of the host cell interactions of MCV and the molecular function of MC159.
Topics: Adaptor Proteins, Signal Transducing; Apoptosis; Autophagy; HEK293 Cells; HeLa Cells; Host-Pathogen Interactions; Humans; Immune Evasion; MCF-7 Cells; Molluscum Contagiosum; Molluscum contagiosum virus; NF-kappa B; Protein Binding; Protein Processing, Post-Translational; Signal Transduction; Viral Proteins; src Homology Domains
PubMed: 30842330
DOI: 10.1128/JVI.01613-18 -
Antimicrobial Agents and Chemotherapy Dec 2014The dermatological disease molluscum contagiosum (MC) presents as lesions restricted solely to the skin. The poxvirus molluscum contagiosum virus (MCV) is responsible...
The dermatological disease molluscum contagiosum (MC) presents as lesions restricted solely to the skin. The poxvirus molluscum contagiosum virus (MCV) is responsible for this skin disease that is easily transmitted through casual contact among all populations, with greater frequency in children and immunosuppressed individuals. In addition, sexual transmission of MCV in adolescents and adults is a health concern. Although the skin lesions ultimately resolve in immunocompetent individuals, they can persist for extended periods, be painful, and result in scarring. Treatment is problematic, and there is no drug that specifically targets MCV. The inability of MCV to propagate in cell culture has impeded drug development. To overcome these barriers, we integrated three new developments. First, we identified a new MCV drug target (mD4) that is essential for processive DNA synthesis in vitro. Second, we discovered a small chemical compound that binds to mD4 and prevents DNA synthesis in vitro. Third, and most significant, we engineered a hybrid vaccinia virus (mD4-VV) in which the natural vaccinia D4 (vD4) gene is replaced by the mD4 target gene. This hybrid virus is dependent on mD4 for viral growth in culture and is inhibited by the small compound. This target system provides, for the first time, a platform and approach for the discovery and evaluation of new therapeutics that can be used to treat MC.
Topics: Animals; Antiviral Agents; Biological Assay; Cell Line; Chlorocebus aethiops; Cloning, Molecular; DNA, Viral; DNA-Directed DNA Polymerase; Drug Discovery; Epithelial Cells; Gene Expression; Humans; Kidney; Molecular Targeted Therapy; Molluscum contagiosum virus; Plasmids; Rabbits; Reassortant Viruses; Recombinant Proteins; Small Molecule Libraries; Vaccinia virus; Viral Proteins
PubMed: 25267668
DOI: 10.1128/AAC.03660-14