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Indian Journal of Ophthalmology Jul 2019
Topics: Diagnosis, Differential; Eye Infections, Viral; Follow-Up Studies; Humans; Keratoconjunctivitis; Male; Molluscum Contagiosum; Molluscum contagiosum virus; Young Adult
PubMed: 31238446
DOI: 10.4103/ijo.IJO_1808_18 -
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 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 -
The British Journal of Dermatology Mar 2019
Topics: Child; Dermoscopy; Female; Humans; Microscopy, Electron, Transmission; Molluscum Contagiosum; Molluscum contagiosum virus; Perineum; Skin
PubMed: 30821395
DOI: 10.1111/bjd.17401 -
Journal of the American Academy of... Mar 2020
Topics: Adult; Child; Dermatologic Surgical Procedures; Humans; Molluscum Contagiosum; Molluscum contagiosum virus; Skin; Surgical Instruments; Treatment Outcome
PubMed: 30797842
DOI: 10.1016/j.jaad.2019.02.042 -
The British Journal of Dermatology Aug 2019
Topics: Adult; Antibodies, Monoclonal, Humanized; Cantharidin; Cryotherapy; Dermatitis, Atopic; Drug Resistance, Viral; Drug Substitution; Humans; Imiquimod; Immunosuppressive Agents; Interleukin-4 Receptor alpha Subunit; Male; Molluscum Contagiosum; Molluscum contagiosum virus; Treatment Outcome
PubMed: 30719708
DOI: 10.1111/bjd.17712 -
Viruses Oct 2018Molluscum contagiosum virus (MCV) is the sole member of the genus and the causative agent of molluscum contagiosum (MC), a common skin disease. Although it is an...
Molluscum contagiosum virus (MCV) is the sole member of the genus and the causative agent of molluscum contagiosum (MC), a common skin disease. Although it is an important and frequent human pathogen, its genetic landscape and evolutionary history remain largely unknown. In this study, ten novel complete MCV genome sequences of the two most common MCV genotypes were determined (five MCV1 and five MCV2 sequences) and analyzed together with all MCV complete genomes previously deposited in freely accessible sequence repositories (four MCV1 and a single MCV2). In comparison to MCV1, a higher degree of nucleotide sequence conservation was observed among MCV2 genomes. Large-scale recombination events were identified in two newly assembled MCV1 genomes and one MCV2 genome. One recombination event was located in a newly identified recombinant region of the viral genome, and all previously described recombinant regions were re-identified in at least one novel MCV genome. MCV genes comprising the identified recombinant segments have been previously associated with viral interference with host T-cell and NK-cell immune responses. In conclusion, the two most common MCV genotypes emerged along divergent evolutionary pathways from a common ancestor, and the differences in the heterogeneity of MCV1 and MCV2 populations may be attributed to the strictness of the constraints imposed by the host immune response.
Topics: Chemotaxis; Computational Biology; Evolution, Molecular; Genetic Variation; Genome, Viral; Genomics; Genotype; High-Throughput Nucleotide Sequencing; Humans; Immunity; Killer Cells, Natural; Molecular Sequence Annotation; Molluscum Contagiosum; Molluscum contagiosum virus; Mosaicism; Phylogeny; Recombination, Genetic; T-Lymphocytes; Viral Load
PubMed: 30373153
DOI: 10.3390/v10110586 -
Cutis Sep 2018Predisposition to cutaneous viral infections is known to be a minor criterion of Hanifin and Rajka's diagnostic standard of atopic dermatitis (AD); however, the causal...
Predisposition to cutaneous viral infections is known to be a minor criterion of Hanifin and Rajka's diagnostic standard of atopic dermatitis (AD); however, the causal relationship between molluscum contagiosum virus (MCV) infection and AD onset or aggravation has not been widely explored. The objective of this study was to identify pediatric patients with AD onset or flare triggered by MCV infection as well as to characterize the setting under which MCV may trigger AD onset or flares in children. Fifty children with prior or current MCV infection presenting sequentially to an outpatient pediatric dermatology practice over a 1-month period were evaluated. Results indicated that children who contract MCV infection may be targets for skin care interventions to prevent and/or control AD.
Topics: Adolescent; Child; Child, Preschool; Dermatitis, Atopic; Female; Humans; Infant; Male; Molluscum Contagiosum; Molluscum contagiosum virus
PubMed: 30372710
DOI: No ID Found -
Journal Der Deutschen Dermatologischen... Sep 2018
Topics: Child; Epidermal Cyst; Humans; Male; Microscopy, Electron, Transmission; Molluscum Contagiosum; Molluscum contagiosum virus
PubMed: 30130000
DOI: 10.1111/ddg.13633 -
Acta Ophthalmologica Aug 2018To describe the different clinical presentations of periocular molluscum contagiosum (MC) lesions and their epidemiological, clinical and histopathological features.
PURPOSE
To describe the different clinical presentations of periocular molluscum contagiosum (MC) lesions and their epidemiological, clinical and histopathological features.
METHODS
Medical records and histopathological sections of all cases of periocular MC treated at the oculoplastic clinic of the Goldschleger Eye Institute, Sheba Medical Center, Israel, between 1995 and 2016 were retrospectively reviewed. The following data were extracted: gender, age at the time of MC diagnosis, immune competency, location of the periocular lesions, number of lesions, dimensions of the lesions, clinical presentation, histopathological features, suspected clinical diagnosis before histopathological diagnosis and treatment.
RESULTS
The series was composed of 41 patients (19 males, 22 females) whose mean age at presentation was 20.41 ± 21.10 years (range 1-71 years). Only one patient was immunosuppressed. The cases were classified into six proposed clinical presentations: 'umbilicated nodular', 'big/giant', 'conglomerated', 'erythematous', 'inflamed' and 'pedunculated'.
CONCLUSION
This is the first time that different clinical types of MC lesions are labelled. The current evidence also indicates that MC lesions should be suspected not only in children and in immunosuppressed adult patients but also in immunocompetent patients of all ages.
Topics: Adolescent; Adult; Aged; Biopsy; Child; Child, Preschool; Diagnosis, Differential; Eye Infections, Viral; Eyelid Diseases; Eyelids; Female; Humans; Infant; Male; Microscopy, Electron; Middle Aged; Molluscum Contagiosum; Molluscum contagiosum virus; Orbit; Retrospective Studies; Young Adult
PubMed: 29855150
DOI: 10.1111/aos.13717