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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 -
Viruses Oct 2021Viral infection activates cellular antiviral defenses including programmed cell death (PCD). Many viruses, particularly those of the family, encode cell death...
Viral infection activates cellular antiviral defenses including programmed cell death (PCD). Many viruses, particularly those of the family, encode cell death inhibitors that antagonize different forms of PCD. While some viral inhibitors are broadly active in cells of different species, others have species-specific functions, probably reflecting the co-evolution of the herpesviruses with their respective hosts. Human cytomegalovirus (HCMV) protein UL36 is a dual cell death pathway inhibitor. It blocks death receptor-dependent apoptosis by inhibiting caspase-8 activation, and necroptosis by binding to the mixed lineage kinase domain-like (MLKL) protein and inducing its degradation. While UL36 has been shown to inhibit apoptosis in human and murine cells, the specificity of its necroptosis-inhibiting function has not been investigated. Here we show that UL36 interacts with both human and murine MLKL, but has a higher affinity for human MLKL. When expressed by a recombinant mouse cytomegalovirus (MCMV), UL36 caused a modest reduction of murine MLKL levels but did not inhibit necroptosis in murine cells. These data suggest that UL36 inhibits necroptosis, but not apoptosis, in a species-specific manner, similar to ICP6 of herpes simplex virus type 1 and MC159 of molluscum contagiosum virus. Species-specific necroptosis inhibition might contribute to the narrow host range of these viruses.
Topics: Animals; Apoptosis; Cell Line; Cytomegalovirus; Herpesviridae; Herpesvirus 1, Human; Host-Pathogen Interactions; Mice; Molluscum contagiosum virus; Muromegalovirus; Necroptosis; Necrosis; Species Specificity; Viral Proteins
PubMed: 34834942
DOI: 10.3390/v13112134 -
Viruses Oct 2021Viral skin infections often affect the sports community. The aim of this study was to assess the rates, location sites, and seasons of appearance of common viral...
Viral skin infections often affect the sports community. The aim of this study was to assess the rates, location sites, and seasons of appearance of common viral cutaneous diseases in beach volleyball athletes in Greece. Five hundred and forty-nine beach volleyball athletes participated in this study. The average age was 28.4 years. The viral infections were herpes simplex (type 1), molluscum contagiosum and warts. The measured parameters included: gender, age, the season when athletes may be more susceptible to infections and the location of infection in the body. Practicing information such as the number of training years, number of weekly trainings, and average hours of daily training was also recorded. Incidence rates correlated in relation to age: (a) warts ( < 0.001), molluscum contagiosum ( < 0.001), and herpes simplex ( = 0.001); (b) years of training: warts ( < 0.001), molluscum contagiosum ( < 0.001), and herpes simplex ( = 0.004); (c) average hours of daily training: molluscum contagiosum ( = 0.006) and herpes simplex ( < 0.010). The skin is the largest organ, and the risk of infection should not be underestimated. Prevention, early detection, recognition, and treatment are related to health and athletic performance, but also to the risk of transmission.
Topics: Adult; Athletes; Female; Greece; Herpes Simplex; Humans; Male; Molluscum Contagiosum; Molluscum contagiosum virus; Phylogeny; Simplexvirus; Skin Diseases; Volleyball; Warts; Young Adult
PubMed: 34834914
DOI: 10.3390/v13112107 -
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 -
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 -
The Journal of General Virology Aug 2020Molluscum contagiosum virus (MCV) is a common cause of benign skin lesions in young children and currently the only endemic human poxvirus. Following the infection of...
Molluscum contagiosum virus (MCV) is a common cause of benign skin lesions in young children and currently the only endemic human poxvirus. Following the infection of primary keratinocytes in the epidermis, MCV induces the proliferation of infected cells and this results in the production of wart-like growths. Full productive infection is observed only after the infected cells differentiate. During this prolonged replication cycle the virus must avoid elimination by the host immune system. We therefore sought to investigate the function of the two major histocompatibility complex class-I-related genes encoded by the MCV genes mc033 and mc080. Following insertion into a replication-deficient adenovirus vector, codon-optimized versions of mc033 and mc080 were expressed as endoglycosidase-sensitive glycoproteins that localized primarily in the endoplasmic reticulum. MC080, but not MC033, downregulated cell-surface expression of endogenous classical human leucocyte antigen (HLA) class I and non-classical HLA-E by a transporter associated with antigen processing (TAP)-independent mechanism. MC080 exhibited a capacity to inhibit or activate NK cells in autologous assays in a donor-specific manner. MC080 consistently inhibited antigen-specific T cells being activated by peptide-pulsed targets. We therefore propose that MC080 acts to promote evasion of HLA-I-restricted cytotoxic T cells.
Topics: Antigen Presentation; CD8-Positive T-Lymphocytes; Cell Line; Down-Regulation; Endoplasmic Reticulum; Histocompatibility Antigens Class I; Host-Pathogen Interactions; Humans; Immune Evasion; Keratinocytes; Killer Cells, Natural; Molluscum contagiosum virus; T-Lymphocytes, Cytotoxic; Viral Proteins
PubMed: 32510303
DOI: 10.1099/jgv.0.001417 -
The Journal of General Virology Mar 2021Cases of pox-like lesions in horses and donkeys have been associated with poxviruses belonging to different genera of the family . These include the orthopoxviruses...
Cases of pox-like lesions in horses and donkeys have been associated with poxviruses belonging to different genera of the family . These include the orthopoxviruses vaccinia virus (VACV), horsepoxvirus (HPXV) and cowpoxvirus (CPXV), as well as a potentially novel parapoxvirus and molluscum contagiosum virus (MOCV). However, with the exception of VACV, HPXV and CPXV, the genomic characterization of the causative agents remains largely elusive with only single short genome fragments available. Here we present the first full-length genome sequence of an equine molluscum contagiosum-like virus (EMCLV) directly determined from skin biopsies of a horse with generalized papular dermatitis. Histopathological analysis of the lesions revealed severe epidermal hyperplasia with numerous eosinophilic inclusion bodies within keratinocytes. Virions were detected in the lesions in embedded tissue by transmission electron microscopy. The genome sequence determined by next- and third-generation sequencing comprises 166 843 nt with inverted terminal repeats (ITRs) of 3473 nt. Overall, 20 of the predicted 159 ORFs have no equivalents in other poxviruses. Intriguingly, two of these ORFs were identified to encode homologues of mammalian proteins involved in immune signalling pathways, namely (SECTM1) and (IGFLR1), that were not described in any virus family so far. Phylogenetic analysis with all relevant representatives of the suggests that EMCLV should be nominated as a new species within the genus .
Topics: Animals; Female; Genome, Viral; High-Throughput Nucleotide Sequencing; Horse Diseases; Horses; Intercellular Signaling Peptides and Proteins; Membrane Proteins; Molluscipoxvirus; Molluscum contagiosum virus; Open Reading Frames; Phylogeny; Poxviridae Infections; Skin; Skin Diseases, Viral; Transcription, Genetic; Viral Proteins; Virus Replication; Whole Genome Sequencing
PubMed: 31922947
DOI: 10.1099/jgv.0.001357 -
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 -
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