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Journal of Virology Apr 1998Molluscum contagiosum virus (MCV), the only member of the Molluscipoxvirus genus, causes benign papules in healthy people but disfiguring lesions in immunocompromised...
Molluscum contagiosum virus (MCV), the only member of the Molluscipoxvirus genus, causes benign papules in healthy people but disfiguring lesions in immunocompromised patients. The sequence of MCV has been completed, revealing that MCV encodes a probable type I topoisomerase enzyme. All poxviruses sequenced to date also encode type I topoisomerases, and in the case of vaccinia virus the topoisomerase has been shown to be essential for replication. Thus, inhibitors of the MCV topoisomerase might be useful as antiviral agents. We have cloned the gene for MCV topoisomerase, overexpressed and purified the protein, and begun to characterize its activities in vitro. Like other eukaryotic type I topoisomerases, MCV topoisomerase can relax both positive and negative supercoils. An analysis of the cleavage of plasmid and oligonucleotide substrates indicates that cleavage by MCV topoisomerase is favored just 3' of the sequence 5' (T/C)CCTT 3', resulting in formation of a covalent bond to the 3' T residue, as with other poxvirus topoisomerases. We identified solution conditions favorable for activity and measured the rate of formation and decay of the covalent intermediate. MCV topoisomerase is sensitive to inhibition by coumermycin A1 (50% inhibitory concentration, 32 microM) but insensitive to five other previously reported topoisomerase inhibitors. This work provides the point of departure for studies of the mechanism of function of MCV topoisomerase and the development of medically useful inhibitors.
Topics: Adenosine Triphosphate; Aminocoumarins; Cloning, Molecular; Coumarins; DNA Topoisomerases, Type I; Enzyme Inhibitors; Genes, Viral; Histidine; Humans; Kinetics; Magnesium; Molluscum contagiosum virus; Mutagenesis, Site-Directed; Plasmids; Recombinant Fusion Proteins; Substrate Specificity; Topoisomerase I Inhibitors
PubMed: 9525670
DOI: 10.1128/JVI.72.4.3401-3406.1998 -
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 -
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 -
Virology May 2013Condylomas are caused by human papillomavirus (HPV), but may in rare cases be "negative for HPV" by PCR. Metagenomic sequencing can be used for an unbiased assessment of...
Condylomas are caused by human papillomavirus (HPV), but may in rare cases be "negative for HPV" by PCR. Metagenomic sequencing can be used for an unbiased assessment of the presence of virus. Ten swab sample pools, each containing four cases of "HPV-negative" condylomas, were subjected to metagenomic sequencing. One pool contained Molluscum contagiosum. Five pools contained HPV, of which three pools contained novel putative HPV-types. The 12 samples in these three pools were sequenced individually. Six of these contained HPV and two contained Molluscum contagiosum. Altogether, 1337 HPV-related reads were detected, representing 23 novel putative Gammapapillomaviruses, 10 established HPV types (genital HPV types 6, 57, 58 and 66, Betapapillomavirus types 5, 105, 124, and Gammapapillomavirus types 50, 130, 150) and two described HPV sequences (KC7 and FA69). Complete genomes of Gammapillomavirus FA69 and SE87 were compiled. Metagenomic sequencing reveals that seemingly "HPV-negative" condylomas contain known and previously unknown HPV types.
Topics: Adolescent; Adult; Condylomata Acuminata; Female; Genome, Viral; Humans; Male; Metagenomics; Middle Aged; Molluscum Contagiosum; Molluscum contagiosum virus; Papillomaviridae; Young Adult
PubMed: 23522725
DOI: 10.1016/j.virol.2013.01.023 -
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 -
Virology Nov 1995Molluscum contagiosum virus (MCV) infects preadolescent children and sexually active adults, frequently causing a disfiguring cutaneous disease in immunosuppressed...
Molluscum contagiosum virus (MCV) infects preadolescent children and sexually active adults, frequently causing a disfiguring cutaneous disease in immunosuppressed HIV-infected individuals. The development of an efficacious treatment regime has been hampered by the failure to replicate the virus in the laboratory. Here we report the first demonstration of MCV replication in an experimental system. In human foreskin grafts to athymic mice, MCV induced morphological changes which were indistinguishable from patient biopsies and included the development and migration of molluscum bodies containing mature virions to the epidermal surface.
Topics: Animals; DNA, Viral; Humans; Infant, Newborn; Male; Mice; Mice, Nude; Molluscum Contagiosum; Molluscum contagiosum virus; Skin; Skin Transplantation; Transplantation, Heterologous; Virion; Virus Replication
PubMed: 7491789
DOI: 10.1006/viro.1995.0037 -
Antimicrobial Agents and Chemotherapy Dec 2014The dermatological disease molluscum contagiosum (MC) presents as lesions restricted solely to the skin. The poxvirus molluscum contagiosum virus (MCV) is responsible...
The dermatological disease molluscum contagiosum (MC) presents as lesions restricted solely to the skin. The poxvirus molluscum contagiosum virus (MCV) is responsible for this skin disease that is easily transmitted through casual contact among all populations, with greater frequency in children and immunosuppressed individuals. In addition, sexual transmission of MCV in adolescents and adults is a health concern. Although the skin lesions ultimately resolve in immunocompetent individuals, they can persist for extended periods, be painful, and result in scarring. Treatment is problematic, and there is no drug that specifically targets MCV. The inability of MCV to propagate in cell culture has impeded drug development. To overcome these barriers, we integrated three new developments. First, we identified a new MCV drug target (mD4) that is essential for processive DNA synthesis in vitro. Second, we discovered a small chemical compound that binds to mD4 and prevents DNA synthesis in vitro. Third, and most significant, we engineered a hybrid vaccinia virus (mD4-VV) in which the natural vaccinia D4 (vD4) gene is replaced by the mD4 target gene. This hybrid virus is dependent on mD4 for viral growth in culture and is inhibited by the small compound. This target system provides, for the first time, a platform and approach for the discovery and evaluation of new therapeutics that can be used to treat MC.
Topics: Animals; Antiviral Agents; Biological Assay; Cell Line; Chlorocebus aethiops; Cloning, Molecular; DNA, Viral; DNA-Directed DNA Polymerase; Drug Discovery; Epithelial Cells; Gene Expression; Humans; Kidney; Molecular Targeted Therapy; Molluscum contagiosum virus; Plasmids; Rabbits; Reassortant Viruses; Recombinant Proteins; Small Molecule Libraries; Vaccinia virus; Viral Proteins
PubMed: 25267668
DOI: 10.1128/AAC.03660-14 -
Skin Therapy Letter 2014Molluscum contagiosum is a poxvirus infection of the skin that is commonly observed in children. The molluscum contagiosum virus (MCV) expresses several gene-products...
Molluscum contagiosum is a poxvirus infection of the skin that is commonly observed in children. The molluscum contagiosum virus (MCV) expresses several gene-products that are involved in its pathogenesis and evasion of the host immune system. MCV can be transmitted both to other sites of the body and to other individuals through direct physical contact as well as fomites. While diagnosis is generally straightforward clinically, management of molluscum contagiosum is controversial. Several treatment options are available for the destruction of individual lesions, but there is insufficient evidence for therapeutic intervention being any more effective than natural, spontaneous resolution. Complex cases, such as infection occurring in immunocompromised patients and in mucocutaneous sites, require an alternative approach to management. Molluscum contagiosum continues to represent a burden on children and parents worldwide.
Topics: Child; Global Health; Humans; Immunocompromised Host; Molluscum Contagiosum; Molluscum contagiosum virus
PubMed: 24740746
DOI: No ID Found -
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 -
PloS One 2014Molluscum contagiosum virus (MCV) causes an innocuous yet persistent skin infection in immunocompetent individuals and is spread by contact with lesions. Studies point...
BACKGROUND
Molluscum contagiosum virus (MCV) causes an innocuous yet persistent skin infection in immunocompetent individuals and is spread by contact with lesions. Studies point to atopic dermatitis (AD) as a risk factor for MCV infection; however, there are no longitudinal studies that have evaluated this hypothesis.
METHODS
Outpatient visit data from fiscal years 2001-2009 for American Indian and Alaska Native (AI/AN) children were examined to describe the incidence of molluscum contagiosum (MC). We conducted a case-control study of patients <5 years old at an Indian Health Service (IHS) clinic to evaluate dermatological risk factors for infection.
RESULTS
The incidence rate for MC in children <5 years old was highest in the West and East regions. MC cases were more likely to have a prior or co-occurring diagnosis of eczema, eczema or dermatitis, impetigo, and scabies (p<0.05) compared to controls; 51.4% of MC cases had a prior or co-occurring diagnosis of eczema or dermatitis.
CONCLUSIONS
The present study is the first demonstration of an association between AD and MC using a case-control study design. It is unknown if the concurrent high incidence of eczema and MC is related, and this association deserves further investigation.
Topics: Ambulatory Care; Case-Control Studies; Child, Preschool; Female; Humans; Incidence; Indians, North American; Infant; Male; Molluscum Contagiosum; Molluscum contagiosum virus; Odds Ratio; Risk Factors; United States
PubMed: 25072249
DOI: 10.1371/journal.pone.0103419