-
Biology Feb 2024is a family of large, complex, enveloped, and double-stranded DNA viruses. The members of this family are ubiquitous and well known to cause contagious diseases in...
is a family of large, complex, enveloped, and double-stranded DNA viruses. The members of this family are ubiquitous and well known to cause contagious diseases in humans and other types of animals as well. Taxonomically, the family is classified into two subfamilies, namely (affecting vertebrates) and (affecting insects). The members of the subfamily are further divided into 18 genera based on the genome architecture and evolutionary relationship. Of these 18 genera, four genera, namely Molluscipoxvirus, Orthopoxvirus, Parapoxvirus, and Yatapoxvirus, are known for infecting humans. Some of the popular members of are variola virus, vaccine virus, Mpox (formerly known as monkeypox), cowpox, etc. There is still a pressing demand for the development of effective vaccines against poxviruses. Integrated immunoinformatics and artificial-intelligence (AI)-based methods have emerged as important approaches to design multi-epitope vaccines against contagious emerging infectious diseases. Despite significant progress in immunoinformatics and AI-based techniques, limited methods are available to predict the epitopes. In this study, we have proposed a unique method to predict the potential antigens and T-cell epitopes for multiple poxviruses. With PoxiPred, we developed an AI-based tool that was trained and tested with the antigens and epitopes of poxviruses. Our tool was able to locate 3191 antigen proteins from 25 distinct poxviruses. From these antigenic proteins, PoxiPred redundantly located up to five epitopes per protein, resulting in 16,817 potential T-cell epitopes which were mostly (i.e., 92%) predicted as being reactive to CD8+ T-cells. PoxiPred is able to, on a single run, identify antigens and T-cell epitopes for poxviruses with one single input, i.e., the proteome file of any poxvirus.
PubMed: 38392343
DOI: 10.3390/biology13020125 -
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 -
Viruses Nov 2023Molluscum contagiosum (MC) is characterized by skin lesions containing the highly contagious molluscum contagiosum poxvirus (MCV). MCV primarily infects children, with...
Molluscum contagiosum (MC) is characterized by skin lesions containing the highly contagious molluscum contagiosum poxvirus (MCV). MCV primarily infects children, with one US Food and Drug Administration (FDA)-approved drug-device treatment in use but no approved medications. Assessing antivirals is hindered by the inability of MCV to replicate in vitro. Here, we use vaccinia virus as a surrogate to provide evidence of the anti-poxvirus properties of berdazimer sodium, a new chemical entity, and the active substance in berdazimer gel, 10.3%, a nitric oxide-releasing topical in phase 3 development for the treatment of MC. We show that berdazimer sodium reduced poxvirus replication and, through a novel methodology, demonstrate that cells infected with drug-treated MCV virions have reduced early gene expression. Specifically, this is accomplished by studying the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB)-blocking protein MC160 as an example of an early gene. The results provide a plausible unique antiviral mechanism of action supporting increased MCV resolution observed in patients treated with berdazimer gel, 10.3% and describe a novel methodology that overcomes limitations in investigating MCV response in vitro to a potential new MC topical medication.
Topics: United States; Child; Humans; Molluscum contagiosum virus; Molluscum Contagiosum; Siloxanes; Antiviral Agents
PubMed: 38140601
DOI: 10.3390/v15122360 -
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 -
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 -
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 -
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 Mar 2023Molluscum contagiosum virus (MCV) is a human-adapted poxvirus that causes a common and persistent yet mild infection characterized by distinct, contagious, papular skin...
Molluscum contagiosum virus (MCV) is a human-adapted poxvirus that causes a common and persistent yet mild infection characterized by distinct, contagious, papular skin lesions. These lesions are notable for having little or no inflammation associated with them and can persist for long periods without an effective clearance response from the host. Like all poxviruses, MCV encodes potent immunosuppressive proteins that perturb innate immune pathways involved in virus sensing, the interferon response, and inflammation, which collectively orchestrate antiviral immunity and clearance, with several of these pathways converging at common signaling nodes. One such node is the regulator of canonical nuclear factor kappa B (NF-κB) activation, NF-κB essential modulator (NEMO). Here, we report that the MCV protein MC008 specifically inhibits NF-κB through its interaction with NEMO, disrupting its early ubiquitin-mediated activation and subsequent downstream signaling. MC008 is the third NEMO-targeting inhibitor to be described in MCV to date, with each inhibiting NEMO activation in distinct ways, highlighting strong selective pressure to evolve multiple ways of disabling this key signaling protein. Inflammation lies at the heart of most human diseases. Understanding the pathways that drive this response is the key to new anti-inflammatory therapies. Viruses evolve to target inflammation; thus, understanding how they do this reveals how inflammation is controlled and, potentially, how to disable it when it drives disease. Molluscum contagiosum virus (MCV) has specifically evolved to infect humans and displays an unprecedented ability to suppress inflammation in our tissue. We have identified a novel inhibitor of human innate signaling from MCV, MC008, which targets NEMO, a core regulator of proinflammatory signaling. Furthermore, MC008 appears to inhibit early ubiquitination, thus interrupting later events in NEMO activation, thereby validating current models of IκB kinase (IKK) complex regulation.
Topics: Humans; NF-kappa B; Molluscum contagiosum virus; Viral Proteins; Signal Transduction; Ubiquitination; I-kappa B Kinase
PubMed: 36916940
DOI: 10.1128/jvi.00108-23 -
Antiviral Research Mar 2023Molluscum contagiosum (MC) is an infectious disease that occurs only in humans with a tropism that is narrowly restricted to the outermost epidermal layer of the skin....
Molluscum contagiosum (MC) is an infectious disease that occurs only in humans with a tropism that is narrowly restricted to the outermost epidermal layer of the skin. Molluscum contagiosum virus (MCV) is the causative agent of MC which produces skin lesions that can persist for months to several years. MCV is efficiently transmitted by direct physical contact or by indirect contact with fomites. MC is most prevalent in children and immune compromised patients. The failure to develop a drug that targets MCV replication has been hampered for decades by the inability to propagate MCV in cell culture. To address this dilemma, we recently engineered a surrogate poxvirus expressing the MCV processivity factor (mD4) as the drug target. The mD4 protein is essential for viral replication by keeping the viral polymerase tethered to the DNA template. In this study we have designed and synthesized a lead compound (7269) that is able to prevent mD4 dependent processive DNA synthesis in vitro (IC = 6.8 μM) and effectively inhibit propagation of the mD4-VV surrogate virus in BSC-1 cells (EC = 13.2 μM) with negligible cytotoxicity. In human liver microsomes, 7269 was shown to be stable for almost 2 h. When tested for penetration into human cadaver skin in a formulated gel, the level of 7269 in the epidermal layer was nearly 100 times the concentration (EC) needed to inhibit propagation of the mD4-VV surrogate virus in BSC-1 cells. The gel formulated 7269 was scored as a non-irritant on skin and shown to have a shelf-life that was completely stable after several months. In summary, 7269 is a potential Lead for becoming the first MCV anti-viral compound to treat MC and thereby, addresses this unmet medical need that has persisted for many decades.
Topics: Child; Humans; Molluscum contagiosum virus; Viral Proteins; Molluscum Contagiosum; DNA
PubMed: 36603771
DOI: 10.1016/j.antiviral.2022.105520