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Clinical Infectious Diseases : An... Jan 2015Some human poxvirus infections can be acquired through zoonotic transmission. We report a previously unknown poxvirus infection in 2 patients, 1 of whom was...
BACKGROUND
Some human poxvirus infections can be acquired through zoonotic transmission. We report a previously unknown poxvirus infection in 2 patients, 1 of whom was immunocompromised; both patients had known equine contact.
METHODS
The patients were interviewed and clinical information was abstracted from the patients' medical files. Biopsies of the skin lesions were collected from both patients for histopathology, immunohistochemistry, and transmission electron microscopy analysis. Oral and skin swabs were collected from animals with frequent contact with the patients, and environmental sampling including rodent trapping was performed on the farm where the immunosuppressed patient was employed. "Pan-pox and high Guanine-cytosine" polymerase chain reaction assays were performed on patient, animal, and environmental isolates. Amplicon sequences of the viral DNA were used for agent identification and phylogenetic analysis.
RESULTS
Specimens from both human cases revealed a novel poxvirus. The agent shares 88% similarity to viruses in the Parapoxvirus genus and 78% to those in the Molluscipoxvirus genus but is sufficiently divergent to resist classification as either. All animal and environmental specimens were negative for poxvirus and both patients had complete resolution of lesions.
CONCLUSIONS
This report serves as a reminder that poxviruses should be considered in cutaneous human infections, especially in individuals with known barnyard exposures. The clinical course of the patients was similar to that of parapoxvirus infections, and the source of this virus is currently unknown but is presumed to be zoonotic. This report also demonstrates the importance of a comprehensive approach to diagnosis of human infections caused by previously unknown pathogens.
Topics: Biopsy; DNA, Viral; Humans; Molecular Sequence Data; Polymerase Chain Reaction; Poxviridae; Poxviridae Infections; Sequence Analysis, DNA; Skin; United States
PubMed: 25301210
DOI: 10.1093/cid/ciu790 -
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 -
Archives of Razi Institute Feb 2023virus (MCV) is an infection caused by the . Antiviral medications used to treat MCV infections have several problems, including drug-resistant and toxicity. As a...
virus (MCV) is an infection caused by the . Antiviral medications used to treat MCV infections have several problems, including drug-resistant and toxicity. As a result, improving safe, innovative, and effective antiviral drugs is critical. Therefore the current study aimed to investigate ZnO-NPs effects on infection and replication, among the main exciting viruses that menace human health. The antiviral activity of zinc oxide nanoparticles (ZnO-NPs) against MCV infection was investigated in this work. FESEM and TEM electron microscopy were used to examine the nanoparticles. The cytotoxicity of the nanoparticles was assessed using the MTT assay, and anti-influenza effects were detected using RT-PCR and TCID50. An indirect immunofluorescence experiment was used to investigate the inhibitory effect of nanoparticles on viral antigen expression. In all tests, acyclovir was employed as a control. Compared to virus control, post-exposure of MCV with ZnO nanoparticles at the highest dose but is not toxic (100 g/mL) resulted in 0.2, 0.9, 1.9, and 2.8 log10 TCID50 reductions in infectious diseases virus titer (P=0.0001). This ZnO-nanoparticles level was accompanied by an inhibition percentage (17.8%, 27.3%, 53.3%, 62.5 %, and 75.9%), respectively, measured based on viral load compared with the virus control. Compared to the positive control, fluorescence emission intensity in virally infected cells that administrated ZnO nanoparticles was statically decreased. Our findings demonstrated that ZnO-NPs have antiviral effects against the MCV. This property indicates that ZnO-NP has a high potential for usage in topical formulations to treat facial and labial lesions.
Topics: Humans; Antiviral Agents; Fluorescent Antibody Technique, Indirect; Molluscum contagiosum virus; Nanoparticles; Zinc Oxide; Molluscum Contagiosum
PubMed: 37312695
DOI: 10.22092/ARI.2022.358496.2236 -
Biochemical and Biophysical Research... Jul 2015Caspase-8 is a key mediator in various biological processes such as apoptosis, necroptosis, inflammation, T/B cells activation, and cell motility. Caspase-8 is...
Caspase-8 is a key mediator in various biological processes such as apoptosis, necroptosis, inflammation, T/B cells activation, and cell motility. Caspase-8 is characterized by the N-terminal tandem death effector domains (DEDs) and the C-terminal catalytic protease domain. The DEDs mediate diverse functions of caspase-8 through homotypic interactions of the DEDs between caspase-8 and its partner proteins. Here, we report the first crystal structure of the DEDs of caspase-8. The overall structure of the DEDs of caspase-8 is similar to that of the DEDs of vFLIP MC159, which is composed of two tandem death effector domains that closely associate with each other in a head-to-tail manner. Structural analysis reveals distinct differences in the region connecting helices α2b and α4b in the second DED of the DEDs between caspase-8 and MC159, in which the helix α3b in MC159 is replaced by a loop in caspase-8. Moreover, the different amino acids in this region might confer the distinct features of solubility and aggregation for the DEDs of caspase-8 and MC159.
Topics: Amino Acid Sequence; Caspase 8; Crystallography, X-Ray; Humans; Models, Molecular; Molecular Sequence Data; Molluscum Contagiosum; Molluscum contagiosum virus; Protein Structure, Tertiary; Sequence Alignment; Viral Proteins
PubMed: 26003730
DOI: 10.1016/j.bbrc.2015.05.054 -
The American Journal of Dermatopathology Aug 2015Langerhans cell histiocytosis (LCH) carries a prognosis, which ranges from benign to potentially fatal. There is currently little framework to decipher metrics, which...
Langerhans cell histiocytosis (LCH) carries a prognosis, which ranges from benign to potentially fatal. There is currently little framework to decipher metrics, which predict the benign versus aggressive nature of LCH. We wanted to determine whether molluscum contagiosum virus (MCV) DNA could be isolated from a cutaneous lesion, demonstrating Langerhans cell hyperplasia resembling LCH in a patient with both. Polymerase chain reaction on biopsy-proven MCV and the hyperplastic lesion has been performed. Two specific regions within the MCV genome were detected from both biopsies. The authors report our findings and suggest that some MCV can produce histological lesions resembling LCH, similar to the literature on scabies mimicking LCH. Efforts to find a reactive "driver" in LCH may significantly inform the clinical scenario.
Topics: Adolescent; Antigens, CD1; DNA, Viral; Histiocytosis, Langerhans-Cell; Humans; Hyperplasia; Langerhans Cells; Male; Molluscum Contagiosum; Molluscum contagiosum virus; S100 Proteins
PubMed: 25140667
DOI: 10.1097/DAD.0000000000000201 -
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 -
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 -
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 -
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