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Viruses Dec 2010Cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, HPMPC] is an acyclic nucleoside analog approved since 1996 for clinical use in the treatment of...
Cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, HPMPC] is an acyclic nucleoside analog approved since 1996 for clinical use in the treatment of cytomegalovirus (CMV) retinitis in AIDS patients. Cidofovir (CDV) has broad-spectrum activity against DNA viruses, including herpes-, adeno-, polyoma-, papilloma- and poxviruses. Among poxviruses, cidofovir has shown in vitro activity against orthopox [vaccinia, variola (smallpox), cowpox, monkeypox, camelpox, ectromelia], molluscipox [molluscum contagiosum] and parapox [orf] viruses. The anti-poxvirus activity of cidofovir in vivo has been shown in different models of infection when the compound was administered either intraperitoneal, intranasal (aerosolized) or topically. In humans, cidofovir has been successfully used for the treatment of recalcitrant molluscum contagiosum virus and orf virus in immunocompromised patients. CDV remains a reference compound against poxviruses and holds potential for the therapy and short-term prophylaxis of not only orthopox- but also parapox- and molluscipoxvirus infections.
PubMed: 21994641
DOI: 10.3390/v2122803 -
Lakartidningen Nov 2016Molluscum contagiosum is a viral infection of the epidermis characterized by skin-colored papules or nodules frequently with a central depression. Atypical variants may...
Molluscum contagiosum is a viral infection of the epidermis characterized by skin-colored papules or nodules frequently with a central depression. Atypical variants may occur, primarily in immunosuppressed individuals. We here report a case of »giant Molluscum contagiosum« in an immunocompetent child. The patient was presented with a fairly smooth nodule of 2 cm in diameter on the ring finger. Molluscipoxvirus-like virus particles were detected by electron microscopy from the nodule, but since the clinical picture was not compatible with MC, next generation sequencing was performed in order to verify the diagnosis. Of the total number of obtained sequences, 25% belonged to molluscipoxvirus (MCV) and de novo assembly revealed three contigs corresponding to 95% of the MCV genome. The assembled genome was compared to previously published sequences of the »major envelope protein« used for genotyping of MCV genus. Several unique single nucleotide polymorphisms were identified, which led us to classify this virus as a new subtype of MCV.
Topics: Child, Preschool; Female; Fingers; High-Throughput Nucleotide Sequencing; Humans; Microscopy, Electron; Molluscum Contagiosum; Molluscum contagiosum virus; Sequence Analysis, DNA
PubMed: 27898140
DOI: No ID Found -
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 -
Viruses Nov 2022That cidofovir, an acyclic nucleoside phosphonate (ANP), was inhibitory to the replication of poxviruses was first demonstrated by De Clercq et al.. That its active...
That cidofovir, an acyclic nucleoside phosphonate (ANP), was inhibitory to the replication of poxviruses was first demonstrated by De Clercq et al.. That its active metabolite, the diphosphate, was found to be inhibitory to the molluscum contagiosum () DNA polymerase was demonstrated by Watanabe and Tamaki. Twelve different independent observations have then indicated that cidofovir administered intravenously, topically or intralesionally is efficacious in the treatment of mostly in immunosuppressed patients.
Topics: Humans; Cidofovir; Molluscum contagiosum virus; Cytosine; Organophosphonates; Molluscum Contagiosum
PubMed: 36366582
DOI: 10.3390/v14112484 -
The Pan African Medical Journal 2019Molluscums contagiosum (MC) are benign skin lesions caused by Molluscipoxvirus, primarily affecting children and young adults. They manly involve the skin and rarely the...
Molluscums contagiosum (MC) are benign skin lesions caused by Molluscipoxvirus, primarily affecting children and young adults. They manly involve the skin and rarely the mucous membranes. Clinical diagnosis is easy, confirmed by histological examination of the lesion. However there is no consensus regarding therapy. Eyelid molluscum contagiosum is rare, posing a problem of differential diagnosis especially when it is isolated as well as a therapeutic problem given the proximity of the eyeball. We report the case of a 7-year old girl with isolated eyelid lesion. The patient underwent lesion excision. Anatomopathological examination showed molluscum contagiosum. This study aims to describe the clinical, therapeutic and evolutionary features of this rare localization of molluscum contagiosum.
Topics: Child; Diagnosis, Differential; Eyelid Diseases; Female; Humans; Molluscum Contagiosum
PubMed: 31312291
DOI: 10.11604/pamj.2019.32.177.18418 -
Experimental and Molecular Pathology Dec 2023Molluscum contagiosum virus (MCV) is a poxvirus that causes benign, persistent skin lesions. MCV encodes a variety of immune evasion molecules to dampen host immune...
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-β. Our model indicates MC160 likely alters the TBK1 signaling complex to decrease IFN-β activation at the molecular intersection of the cGAS/STING and MAVS signaling pathways.
Topics: Humans; Molluscum contagiosum virus; HEK293 Cells; Viral Proteins; Nucleotidyltransferases; Immunity, Innate; Interferon-beta; Interferons
PubMed: 37890651
DOI: 10.1016/j.yexmp.2023.104876 -
Journal of the American Academy of... Feb 2024
Topics: Humans; Molluscum Contagiosum; Molluscum contagiosum virus
PubMed: 37871806
DOI: 10.1016/j.jaad.2023.10.033 -
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 -
MBio Nov 2023Four molluscum contagiosum virus (MOCV) genotypes (MOCV1-4) and four subtype variants (MOCV1p, MOCV1va, MOCV1vb, and MOCV1vc) were partially characterized using...
Comprehensive analysis of 66 complete molluscum contagiosum virus (MOCV) genomes: characterization and functional annotation of 47 novel complete MOCV genomes, including the first genome of MOCV genotype 3, and a proposal for harmonized MOCV genotyping indexing.
Four molluscum contagiosum virus (MOCV) genotypes (MOCV1-4) and four subtype variants (MOCV1p, MOCV1va, MOCV1vb, and MOCV1vc) were partially characterized using restriction enzyme profiling in the early 1980s/1990s. However, complete genome sequences of only MOCV1 and MOCV2 are available. The evolutionary pathways of MOCV genotypes and subtype variants with unavailable sequences remain unclear, and also whether all MOCV genotypes/subtype variants can be reliably detected and appropriately categorized using available PCR-based protocols. We fully characterized and functionally annotated 47 complete MOCV genomes, including two putative non-MOCV1/2 isolates, expanding the number of fully characterized MOCV genomes to 66. To ascertain the placement of any putative novel MOCV sequence into the restriction profiling typing scheme, we developed an original framework for extracting complete MOCV genome sequence-based restriction profiles and matching them with reference restriction profiles. We confirmed that two putative non-MOCV1/2 isolates represent the first complete genomes of MOCV3. Comprehensive phylogenomic, recombination, and restriction enzyme recognition site analysis of all 66 currently available MOCV genomes showed that they can be agglomerated into six phylogenetic subgroups (PG1-6), corresponding to the subtype variants from the pioneering studies. PG5 was a novel subtype variant of MOCV2, but no PGs corresponded to the subtype variants MOCV1vb or MOCV4. We showed that the phylogenetic subgroups may have diverged from the prototype MOCV genotype lineages following large-scale recombination events and hinted at partial sequence content of MOCV4 and direction of recombinant transfer in the events that spawned PG5 and the yet undetected subtype variant MOCV1vb.IMPORTANCEFour molluscum contagiosum virus (MOCV) genotypes (MOCV1-4) and four subtype variants were partially characterized using restriction enzyme profiling in the 1980s/1990s, but complete genome sequences of only MOCV1 and MOCV2 are available. The evolutionary pathways whereby genotypes/subtype variants with unavailable sequences emerged and whether all MOCVs can be detected using current diagnostic approaches remain unclear. We fully characterized 47 novel complete MOCV genomes, including the first complete MOCV3 genome, expanding the number of fully characterized genomes to 66. For reliably classifying the novel non-MOCV1/2 genomes, we developed and validated a framework for matching sequence-derived restriction maps with those defining MOCV subtypes in pioneering studies. Six phylogenetic subgroups (PG1-6) were identified, PG5 representing a novel MOCV2 subtype. The phylogenetic subgroups diverged from the prototype lineages following large-scale recombination events and hinted at partial sequence content of MOCV4 and direction of recombinant transfer in the events spawning PG5 and yet undetected MOCV1vb variant.
PubMed: 37947415
DOI: 10.1128/mbio.02224-23 -
Journal of Virology Aug 2017Molluscum contagiosum virus (MCV), the only known extant human-adapted poxvirus, causes a long-duration infection characterized by skin lesions that typically display an...
Molluscum contagiosum virus (MCV), the only known extant human-adapted poxvirus, causes a long-duration infection characterized by skin lesions that typically display an absence of inflammation despite containing high titers of live virus. Despite this curious presentation, MCV is very poorly characterized in terms of host-pathogen interactions. The absence of inflammation around MCV lesions suggests the presence of potent inhibitors of human antiviral immunity and inflammation. However, only a small number of MCV immunomodulatory genes have been characterized in detail. It is likely that many more remain to be discovered, given the density of such sequences in other poxvirus genomes. NF-κB activation occurs in response to both virus-induced pattern recognition receptor (PRR) signaling and cellular activation by virus-induced proinflammatory cytokines like tumor necrosis factor and interleukin-1. Activated NF-κB drives cytokine and interferon gene expression, leading to inflammation and virus clearance. We report that MC005, which has no orthologs in other poxvirus genomes, is a novel inhibitor of PRR- and cytokine-stimulated NF-κB activation. MC005 inhibited NF-κB proximal to the IκB kinase (IKK) complex, and unbiased affinity purification revealed that MC005 interacts with the IKK subunit NEMO (NF-κB essential modulator). MC005 binding to NEMO prevents the conformational priming of the IKK complex that occurs when NEMO binds to ubiquitin chains during pathway activation. These data reveal a novel mechanism of poxvirus inhibition of human innate immunity, validate current dynamic models of NEMO-dependent IKK complex activation, and further clarify how the human-adapted poxvirus MCV can so effectively evade antiviral immunity and suppress inflammation to persist in human skin lesions. Poxviruses adapt to specific hosts over time, evolving and tailoring elegantly precise inhibitors of the rate-limiting steps within the signaling pathways that control innate immunity and inflammation. These inhibitors reveal new features of the antiviral response, clarify existing models of signaling regulation while offering potent new tools for approaching therapeutic intervention in autoimmunity and inflammatory disease. Molluscum contagiosum virus (MCV) is the only known extant poxvirus specifically adapted to human infection and appears adept at evading normal human antiviral responses, yet it remains poorly characterized. We report the identification of MCV protein MC005 as an inhibitor of the pathways leading to the activation of NF-κB, an essential regulator of innate immunity. Further, identification of the mechanism of inhibition of NF-κB by MC005 confirms current models of the complex way in which NF-κB is regulated and greatly expands our understanding of how MCV so effectively evades human immunity.
Topics: Animals; Cell Line; Host-Pathogen Interactions; Humans; I-kappa B Kinase; Immune Evasion; Molluscum contagiosum virus; NF-kappa B; Viral Proteins
PubMed: 28490597
DOI: 10.1128/JVI.00545-17