The Molluscum Contagiosum Gene MC021L Partially Compensates for the Loss of Its Vaccinia Virus Homolog, F13L

Monticelli, Stephanie R.; Bryk, Peter; Ward, Brian M.

doi:10.1128/jvi.01496-20

Cited by 3 publications

(15 citation statements)

References 75 publications

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“…A previous report from our lab determined that vMC021L-HA had similar replication kinetics as vF13L-HA, but produced a small plaque phenotype and EV that incorporated more MC021-HA compared to its homolog, F13-HA [ 28 ]. Glycoproteins, A33, A34, and B5, play multiple roles in EV target cell binding and outer membrane dissolution [ 22 , 23 , 43 , 44 ], and deletion or alteration of the incorporation of these glycoproteins results in the production of EV that are less infectious [ 16 , 17 , 19 , 20 , 22 , 23 , 43 , 44 , 45 – 47 ].…”

Section: Resultsmentioning

confidence: 99%

“…The previous results suggest that an increased amount of F13-HA/MC021-HA, A33, and B5 was incorporated in the outer membrane of EV produced by vMC021L-HA, even though this virus exhibits a small plaque phenotype (Fig 1B) [28]. Therefore, a flow virometry assay was used to quantitatively examine glycoprotein incorporation for individual EV (Fig 2) [41,42].…”

Section: Plos Pathogensmentioning

confidence: 98%

“…vF13L-HA and vΔF13L were generously provided by Bernard Moss (National Institutes of Health, Bethesda), and their generation has been described previously [26,[88][89][90]. vMC021L-HA has been described previously [28]. vF13L-HA/A4L-mCherry and vΔF13L/ A4-mCherry have been described previously [27].…”

Section: Viruses and Infectionsmentioning

confidence: 99%

“…High and low MOI growth curves showed that vMC021L had similar growth kinetics compared to vF13L-HA but spreads slower in cell monolayers. Furthermore, similar levels of EV were produced by vMC021L-HA compared to vF13L-HA but the EV were less infectious [28]. Here, to further investigate the impact of MC021-HA expression on EV production, a novel flow virometry assay was used to reveal that MC021 increased the number of glycoproteins incorporated into released EV [29][30][31][32][33][34][35][36][37][38][39][40][41][42].…”

Section: Introductionmentioning

confidence: 99%

“…To gain a greater insight into the molecular function of F13, a recombinant VACV was created that replaced F13L with its homolog from molluscum contagiosum virus, MC021L [ 28 ]. The resulting virus, vMC021L-HA, has a plaque phenotype significantly smaller than its counterpart, vF13L-HA, but slightly larger than a full F13L deletion (vΔF13L) [ 28 ]. High and low MOI growth curves showed that vMC021L had similar growth kinetics compared to vF13L-HA but spreads slower in cell monolayers.…”

Section: Introductionmentioning

confidence: 99%

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An increase in glycoprotein concentration on extracellular virions dramatically alters vaccinia virus infectivity and pathogenesis without impacting immunogenicity

et al. 2021

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The extracellular virion (EV) form of Orthopoxviruses is required for cell-to-cell spread and pathogenesis, and is the target of neutralizing antibodies in the protective immune response. EV have a double envelope that contains several unique proteins that are involved in its intracellular envelopment and/or subsequent infectivity. One of these, F13, is involved in both EV formation and infectivity. Here, we report that replacement of vaccinia virus F13L with the molluscum contagiosum virus homolog, MC021L results in the production of EV particles with significantly increased levels of EV glycoproteins, which correlate with a small plaque phenotype. Using a novel fluorescence-activated virion sorting assay to isolate EV populations based on glycoprotein content we determine that EV containing either higher or lower levels of glycoproteins are less infectious, suggesting that there is an optimal concentration of glycoproteins in the outer envelope that is required for maximal infectivity of EV. This optimal glycoprotein concentration was required for lethality and induction of pathology in a cutaneous model of animal infection, but was not required for induction of a protective immune response. Therefore, our results demonstrate that there is a sensitive balance between glycoprotein incorporation, infectivity, and pathogenesis, and that manipulation of EV glycoprotein levels can produce vaccine vectors in which pathologic side effects are attenuated without a marked diminution in induction of protective immunity.

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Section: Resultsmentioning

confidence: 99%

Section: Plos Pathogensmentioning

confidence: 98%

Section: Viruses and Infectionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

An increase in glycoprotein concentration on extracellular virions dramatically alters vaccinia virus infectivity and pathogenesis without impacting immunogenicity

et al. 2021

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Exploring the key genomic variation in monkeypox virus during the 2022 outbreak

Zhu,

Yu,

Qin

et al. 2023

BMC Genom Data

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Background In 2022, a global outbreak of monkeypox occurred with a significant shift in its epidemiological characteristics. The monkeypox virus (MPXV) belongs to the B.1 lineage, and its genomic variations that were linked to the outbreak were investigated in this study. Previous studies have suggested that viral genomic variation plays a crucial role in the pathogenicity and transmissibility of viruses. Therefore, understanding the genomic variation of MPXV is crucial for controlling future outbreaks. Methods This study employed bioinformatics and phylogenetic approaches to evaluate the key genomic variation in the B.1 lineage of MPXV. A total of 979 MPXV strains were screened, and 212 representative strains were analyzed to identify specific substitutions in the viral genome. Reference sequences were constructed for each of the 10 lineages based on the most common nucleotide at each site. A total of 49 substitutions were identified, with 23 non-synonymous substitutions. Class I variants, which had significant effects on protein conformation likely to affect viral characteristics, were classified among the non-synonymous substitutions. Results The phylogenetic analysis revealed 10 relatively monophyletic branches. The study identified 49 substitutions specific to the B.1 lineage, with 23 non-synonymous substitutions that were classified into Class I, II, and III variants. The Class I variants were likely responsible for the observed changes in the characteristics of circulating MPXV in 2022. These key mutations, particularly Class I variants, played a crucial role in the pathogenicity and transmissibility of MPXV. Conclusion This study provides an understanding of the genomic variation of MPXV in the B.1 lineage linked to the recent outbreak of monkeypox. The identification of key mutations, particularly Class I variants, sheds light on the molecular mechanisms underlying the observed changes in the characteristics of circulating MPXV. Further studies can focus on functional domains affected by these mutations, enabling the development of effective control strategies against future monkeypox outbreaks.

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The Antiviral Effect of Berdazimer Sodium on Molluscum Contagiosum Virus Using a Novel In Vitro Methodology

Ward,

Riccio,

Cartwright

et al. 2023

Viruses

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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.

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The Molluscum Contagiosum Gene MC021L Partially Compensates for the Loss of Its Vaccinia Virus Homolog, F13L

Cited by 3 publications

References 75 publications

An increase in glycoprotein concentration on extracellular virions dramatically alters vaccinia virus infectivity and pathogenesis without impacting immunogenicity

An increase in glycoprotein concentration on extracellular virions dramatically alters vaccinia virus infectivity and pathogenesis without impacting immunogenicity

Exploring the key genomic variation in monkeypox virus during the 2022 outbreak

The Antiviral Effect of Berdazimer Sodium on Molluscum Contagiosum Virus Using a Novel In Vitro Methodology

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