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Acta Virologica 2019Molluscum contagiosum is a common, self-limiting infectious disease of the skin caused by molluscum contagiosum virus (MCV). The disease primarily affects children,...
Molluscum contagiosum is a common, self-limiting infectious disease of the skin caused by molluscum contagiosum virus (MCV). The disease primarily affects children, sexually active adults, and immunocompromised individuals. Transmission of the virus occurs by direct skin contact. Therefore, the virus is usually detected in the skin and genitals of patients. However, the diagnosis of intracranial infection by the virus is difficult if the skin/mucosa lessons are atypical or absent, and the presence of the virus in the cerebrospinal fluid has not been reported. We report a very rare case of intracranial infection by molluscum contagiosum virus. A 25-year-old girl was admitted to our hospital due to severe headache but no fever or other symptoms. Upon examination, some small flesh-colored flattened papules on both arms were noticed. Blood tests showed slightly reduced levels of CD3 and CD4 T lymphocytes. Three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) and head magnetic resonance (MR) were both normal. Lumbar puncture was performed, and metagenomic sequencing was applied to the spinal fluid. The unique sequences of the molluscum contagiosum virus were identified in the fluid. The patient was then diagnosed with intracranial molluscum contagiosum virus infection. No special treatment was given. The headache gradually disappeared, and the patient was discharged. During our quarterly follow-up, the girl appeared normal, and her skin lesions disappeared. However, her CD3 and CD4 T lymphocyte counts were still slightly lower than the normal level. Our case shows that the application of metagenomic sequencing to cerebrospinal fluid is a sensitive and powerful means to detect pathogens causing intracranial infection. Keywords: Molluscum contagiosum; intracranial infection; metagenomics sequencing.
Topics: Adult; CD4-Positive T-Lymphocytes; Female; Humans; Lymphocyte Count; Metagenomics; Molluscum Contagiosum; Molluscum contagiosum virus; Skin
PubMed: 31507201
DOI: 10.4149/av_2019_313 -
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 -
Journal of Virology Dec 2015Molluscum contagiosum virus (MCV) gene MC159 encodes a viral FLICE inhibitory protein (vFLIP) that inhibits caspase-8-mediated apoptosis. The MC159 protein was also...
UNLABELLED
Molluscum contagiosum virus (MCV) gene MC159 encodes a viral FLICE inhibitory protein (vFLIP) that inhibits caspase-8-mediated apoptosis. The MC159 protein was also reported to inhibit programmed necrosis (necroptosis) and modulate NF-κB activation by interacting with RIP1 and NEMO. The importance of MC159 during MCV infection has remained unknown, as there is no system for propagation and genetic manipulation of this virus. Here we investigated the functions of MC159 during viral infection using murine cytomegalovirus (MCMV) as a surrogate virus. MC159 was inserted into the MCMV genome, replacing M36 or M45, two MCMV genes with functions similar to those reported for MC159. M36 encodes a viral inhibitor of caspase-8-induced apoptosis (vICA) and M45 a viral inhibitor of RIP activation (vIRA), which inhibits RIP1/RIP3-mediated necroptosis. The M45 protein also blocks NF-κB activation by interacting with NEMO. When expressed by MCMV, MC159 blocked tumor necrosis factor alpha (TNF-α)-induced apoptosis of infected cells and partially restored MCMV replication in macrophages. However, MC159 did not fully replace M45, as it did not inhibit necroptosis in murine cells, but it reduced TNF-α-induced necroptosis in MCMV-infected human HT-29 cells. MC159 also differed from M45 in its effect on NF-κB. While MCMV-encoded M45 blocked NF-κB activation by TNF-α and interleukin-1β (IL-1β), MC159 inhibited TNF-α- but not IL-1β-induced NF-κB activation in infected mouse fibroblasts. These results indicate that the spectrum of MC159's functions differs depending on cell type and expression system and that a cell culture system for the propagation of MCV is needed to determine the biological relevance of presumed viral gene functions.
IMPORTANCE
MCV is a human-pathogenic poxvirus that cannot be propagated in cell culture or laboratory animals. Therefore, MCV gene products have been studied predominantly in cells expressing individual viral genes. In this study, we analyzed the function of the MCV gene MC159 by expressing it from a different virus and comparing its functions to those of two well-characterized MCMV genes. In this system, MC159 displayed some but not all of the previously described functions, suggesting that the functions of a viral gene depend on the conditions under which it is expressed. Until a cell culture system for the analysis of MCV becomes available, it might be necessary to analyze MCV genes in several different systems to extrapolate their biological importance.
Topics: Animals; Apoptosis Regulatory Proteins; Cell Line; Cell Survival; Humans; Immunologic Factors; Mice; Molluscum contagiosum virus; Muromegalovirus; Recombinant Proteins; Viral Proteins
PubMed: 26719271
DOI: 10.1128/JVI.02729-15 -
Journal of Virology Aug 2015Molluscum contagiosum virus (MCV) is unique in being the only known extant, human-adapted poxvirus, yet to date, it is very poorly characterized in terms of...
Molluscum contagiosum virus (MCV) is unique in being the only known extant, human-adapted poxvirus, yet to date, it is very poorly characterized in terms of host-pathogen interactions. MCV causes persistent skin lesions filled with live virus, but these are generally immunologically silent, suggesting the presence of potent inhibitors of human antiviral immunity and inflammation. Fewer than five MCV immunomodulatory genes have been characterized in detail, but it is likely that many more remain to be discovered given the density of such sequences in all well-characterized poxviruses. Following virus infection, NF-B activation occurs in response to both pattern recognition receptor (PRR) signaling and cellular activation by virus-elicited proinflammatory cytokines, such as tumor necrosis factor (TNF). As such, NF-B activation is required for virus detection, antiviral signaling, inflammation, and clearance of viral infection. Hence, we screened a library of MCV genes for effects on TNF-stimulated NF-B activation. This revealed MC132, a unique protein with no orthologs in other poxviral genomes, as a novel inhibitor of NF-B. Interestingly, MC132 also inhibited PRR- and virus-activated NF-B, since MC132 interacted with the NF-B subunit p65 and caused p65 degradation. Unbiased affinity purification to identify host targets of MC132 revealed that MC132 acted by targeting NF-B p65 for ubiquitin-dependent proteasomal degradation by recruiting p65 to a host Cullin-5/Elongin B/Elongin C complex. These data reveal a novel mechanism for poxviral inhibition of human innate immunity and further clarify how the human-adapted poxvirus MCV can so effectively evade antiviral immunity to persist in skin lesions.
Topics: Chromatography, Liquid; Enzyme-Linked Immunosorbent Assay; Humans; Immune Tolerance; Immunity, Innate; Immunoblotting; Immunoprecipitation; Microscopy, Confocal; Molluscum contagiosum virus; NF-kappa B; Oligonucleotides; Proteolysis; RNA Interference; Real-Time Polymerase Chain Reaction; Receptors, Pattern Recognition; Tandem Mass Spectrometry; Viral Proteins; eIF-2 Kinase
PubMed: 26041281
DOI: 10.1128/JVI.00799-15 -
Clinical and Experimental Dermatology Dec 2017
Clinical Trial
Topics: Administration, Topical; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Linoleic Acids; Male; Molluscum Contagiosum; Molluscum contagiosum virus; Oenothera biennis; Outcome Assessment, Health Care; Plant Oils; Skin; gamma-Linolenic Acid
PubMed: 28940438
DOI: 10.1111/ced.13226 -
The Journal of Dermatology Jan 2017Immunohistochemical studies of one typical and two atypical cases of molluscum contagiosum with anti-CD34 monoclonal antibodies showed a tightly enclosing fine...
Immunohistochemical studies of one typical and two atypical cases of molluscum contagiosum with anti-CD34 monoclonal antibodies showed a tightly enclosing fine vasculature around the lesional masses of the disease. The thin interstitial septa between the lobules of the molluscum lesions also contained abundant endothelium. An electron microscopic study of a pinched-off lesion of common molluscum contagiosum demonstrated that the tightly enclosing blood vessels lacked muscle layers, suggesting that they were capillaries, being a distance of several hundred nanometers from the basal cells of the molluscum mass. A 3D constructed image of the vasculature confirmed a network of the vessels. These tightly enclosing vascular networks around the lesions of molluscum contagiosum support the rapid growth of this disease.
Topics: Adolescent; Antigens, CD34; Capillaries; Child, Preschool; Dermoscopy; Female; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Immunohistochemistry; Microscopy, Electron; Molluscum Contagiosum; Molluscum contagiosum virus; Skin
PubMed: 27607603
DOI: 10.1111/1346-8138.13519 -
Diagnostic Cytopathology Sep 2021
Topics: Adult; Child, Preschool; Cytodiagnosis; Female; Humans; Male; Middle Aged; Molluscum Contagiosum; Molluscum contagiosum virus; Skin; Young Adult
PubMed: 34251093
DOI: 10.1002/dc.24819 -
Antiviral Research Jun 2024We recently developed compound FC-7269 for targeting the Molluscum contagiosum virus processivity factor (mD4) and demonstrated its ability to inhibit viral processive...
We recently developed compound FC-7269 for targeting the Molluscum contagiosum virus processivity factor (mD4) and demonstrated its ability to inhibit viral processive DNA synthesis in vitro and cellular infection of an mD4-dependent virus (Antiviral Res 211, 2023,105520). However, despite a thorough medicinal chemistry campaign we were unable to generate a potent second analog as a requisite for drug development. We overcame this impasse, by conjugating a short hydrophobic trivaline peptide to FC-7269 to produce FC-TriVal-7269 which significantly increased antiviral potency and reduced cellular toxicity.
Topics: Antiviral Agents; Molluscum contagiosum virus; Humans; Virus Replication; Molluscum Contagiosum; Oligopeptides; Animals; Cell Line
PubMed: 38705201
DOI: 10.1016/j.antiviral.2024.105899 -
Multiple Sclerosis (Houndmills,... Jun 2016Fingolimod-related viral infections have been described on several occasions since its introduction in 2010. We hereby add a report on an otherwise immunocompetent,...
Fingolimod-related viral infections have been described on several occasions since its introduction in 2010. We hereby add a report on an otherwise immunocompetent, 18-year old Caucasian man with relapsing-remitting multiple sclerosis who developed a protracted and extensive molluscum contagiosum (MC) virus infection shortly after being started on fingolimod. Wide-spread cutaneous MC infections in adult patients are considered indicative of underlying immunosuppression. Neurologists prescribing fingolimod ought to be aware of a possibly increased risk of MC, but also need to know about its relative benignity, lack of extra-cutaneous complications, and adequate treatment options.
Topics: Adolescent; Biopsy; Fingolimod Hydrochloride; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Molluscum Contagiosum; Molluscum contagiosum virus; Multiple Sclerosis, Relapsing-Remitting; Opportunistic Infections; Risk Factors
PubMed: 26860987
DOI: 10.1177/1352458516629560 -
Expert Review of Anti-infective Therapy Oct 2014CMX001 (hexadecyloxypropyl-cidofovir, Brincidofovir) is a broad spectrum, lipid conjugate of cidofovir that is converted intracellularly into the active antiviral,...
CMX001 (hexadecyloxypropyl-cidofovir, Brincidofovir) is a broad spectrum, lipid conjugate of cidofovir that is converted intracellularly into the active antiviral, cidofovir diphosphate. The lipid conjugation results in oral bioavailability, higher intracellular concentrations of active drug, lower plasma concentrations of cidofovir and increased antiviral potency against dsDNA viruses.
Topics: Adenoviridae; Antiviral Agents; Cytomegalovirus; Cytosine; DNA Virus Infections; Humans; Microbial Sensitivity Tests; Molluscum contagiosum virus; Organophosphonates; Orthopoxvirus; Polyomavirus
PubMed: 25120093
DOI: 10.1586/14787210.2014.948847