4. Singh SK, ed. Diagnostics to Pathogenomics of Sexually Transmitted Infections. New York: Wiley-Blackwell; 2018.
5. Centers for Disease Control and Prevention. Long term effects. Available at: https://www.cdc.gov/poxvirus/molluscum-contagiosum/long-term-effects. html. Accessed August 31, 2022.
6. Leung AKC, Barankin B, Hon KLE. Molluscum contagiosum: An update. Recent Pat Inflamm Allergy Drug Discov. 2017;11(1):22-31.
7. Chen X, Anstey AV, Bugert JJ. Molluscum contagiosum virus infection. Lancet Infect Dis. 2013;13(10):877-888.
8. Shisler JL. Immune evasion strategies of molluscum contagiosum virus. Adv Virus Res. 2015;92:201-252.
9. Na CH, Kim DJ, Kim MS, et al. Successful treatment of molluscum contagiosum with intralesional immunotherapy by measles, mumps, and rubella vaccine: a report of two cases. Dermatol Ther. 2014;27(6):373-376.
10. Smith KJ, Skelton H. Molluscum Contagiosum. Am J Clin Dermatol. 2002;3(8):535-545.
11. Biswas S, Smith GL, Roy EJ, et al. A comparison of the effect of molluscum contagiosum virus MC159 and MC160 proteins on vaccinia virus virulence in intranasal and intradermal infection routes. J Gen Virol. 2018;99(2):246-252.
12. Douglass NJ, Blake NW, Cream JJ, et al. Similarity in genome organization between molluscum contagiosum virus (MCV) and vaccinia virus (VV): identification of MCV homologues of the VV genes for protein kinase 2, structural protein VP8, RNA polymerase 35 kDa subunit and 3betahydroxysteroid dehydrogenase. J Gen Virol. 1996;77 ( Pt 12):3113-3120.
13. Brady G, Haas DA, Farrell PJ, et al. Molluscum contagiosum virus protein MC005 inhibits NF-κB activation by targeting NEMO-regulated IκB kinase activation. J Virol. 2017;91(15). doi:10.1128/JVI.00545-17
14. Bugert JJ, Darai G. Recent advances in molluscum contagiosum virus research. Arch Virol Suppl. 1997;13:35-47.
15. Senkevich TG, Koonin EV, Bugert JJ, et al. The genome of molluscum contagiosum virus: analysis and comparison with other poxviruses. Virology. 1997;233(1):19-42.
16. Maeda-Chubachi T, Hebert D, Messersmith E, et al. SB206, a nitric oxidereleasing topical medication, induces the beginning of the end sign and molluscum clearance. JID Innov. 2021;1(3):100019.
17. Olsen JR, Gallacher J, Finlay AY, et al. Time to resolution and effect on quality of life of molluscum contagiosum in children in the UK: a prospective community cohort study. Lancet Infect Dis. 2015;15(2):190-195.
18. Molluscum contagiosum: Diagnosis and treatment. Accessed August 31, 2022. https://www.aad.org/public/diseases/a-z/molluscum-contagiosumtreatment
19. Butala N, Siegfried E, Weissler A. Molluscum BOTE sign: a predictor of imminent resolution. Pediatrics. 2013;131(5):e1650-e1653.
20. Institute of Medicine (US) Committee on the Assessment of Future Scientific Needs for Live Variola Virus. Clinical Features of Smallpox. National Academies Press (US); 1999.
21. Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol. 2009;1(6):a001651.
22. Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2. doi:10.1038/sigtrans.2017.
23. Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol. 2014;5:461.
24. Lei V, Petty AJ, Atwater AR, et al. Skin viral infections: host antiviral innate immunity and viral immune evasion. Front Immunol. 2020;11:593901.
25. Hayden MS, Ghosh S. Regulation of NF-κB by TNF family cytokines. Semin Immunol. 2014;26(3):253-266.
26. Brady G, Haas DA, Farrell PJ, et al. Poxvirus protein mc132 from molluscum contagiosum virus inhibits nf-b activation by targeting p65 for degradation. J Virol. 2015;89(16):8406-8415.
27. Tran K, Merika M, Thanos D. Distinct functional properties of IkappaB alpha and IkappaB beta. Mol Cell Biol. 1997;17(9):5386-5399. 28. Nichols DB, Shisler JL. The MC160 protein expressed by the dermatotropic poxvirus molluscum contagiosum virus prevents tumor necrosis factor alpha-induced NF-kappaB activation via inhibition of I kappa kinase complex formation. J Virol. 2006;80(2):578-586.
29. Randall CMH, Jokela JA, Shisler JL. The MC159 protein from the molluscum contagiosum poxvirus inhibits NF-κB activation by interacting with the IκB kinase complex. J Immunol. 2012;188(5):2371-2379.
30. Biswas S, Shisler JL. Molluscum contagiosum virus MC159 abrogates cIAP1-NEMO interactions and inhibits NEMO polyubiquitination. J Virol. 2017;91(15). doi:10.1128/JVI.00276-17
31. Thurau M, Everett H, Tapernoux M, et al. The TRAF3-binding site of human molluscipox virus FLIP molecule MC159 is critical for its capacity to inhibit Fas-induced apoptosis. Cell Death Differ. 2006;13(9):1577-1585.
32. Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev. 2001;14(4):778-809.
33. Randall CMH, Biswas S, Selen CV, et al. Inhibition of interferon gene activation by death-effector domain-containing proteins from the molluscum contagiosum virus. Proc Natl Acad Sci U S A. 2014;111(2):E265-E272.
34. De Martini W, Coutu J, Bugert J, et al. The molluscum contagiosum virus protein MC163 inhibits TNF-α-induced NF-κB activation. Future Virol. 2019;14(5):319-333.
35. Seton Hall University. Characterization of Immune Evasion Properties of the Molluscum Contagiosum Virus MC163 Protein. Available at: https:// scholarship.shu.edu/dissertations/2704. Accessed August 22, 2022.
36. Coutu J, Ryerson MR, Bugert J, et al. The molluscum contagiosum virus protein MC163 localizes to the mitochondria and dampens mitochondrial mediated apoptotic responses. Virology. 2017;505:91-101.
37. Dinarello CA, Novick D, Kim S, et al. Interleukin-18 and IL-18 binding protein. Front Immunol. 2013;4:289.
38. Xiang Y, Moss B. IL-18 binding and inhibition of interferon γ induction by human poxvirus-encoded proteins. Proc Natl Acad Sci. 1999;96(20):11537- 11542.
39. Xiang Y, Moss B. Correspondence of the functional epitopes of poxvirus and human interleukin-18-binding proteins. J Virol. 2001;75(20):9947-9954.
40. Lüttichau HR, Gerstoft J, Schwartz TW. MC148 encoded by human molluscum contagiosum poxvirus is an antagonist for human but not murine CCR8. J Leukoc Biol. 2001;70(2):277-282.
41. Damon I, Murphy PM, Moss B. Broad spectrum chemokine antagonistic activity of a human poxvirus chemokine homolog. Proc Natl Acad Sci U S A. 1998;95(11):6403-6407.
42. Mohr S, Grandemange S, Massimi P, et al. Targeting the retinoblastoma protein by MC007L, gene product of the molluscum contagiosum virus: detection of a novel virus-cell interaction by a member of the poxviruses. J Virol. 2008;82(21):10625-10633.
43. Ahlander J, Bosco G. The RB/E2F pathway and regulation of RNA processing. Biochem Biophys Res Commun. 2009;384(3):280-283. 44. Lee S, Lee EK, Kang DH, et al. Glutathione peroxidase-1 regulates ASK1- dependent apoptosis via interaction with TRAF2 in RIPK3-negative cancer cells. Exp Mol Med. 2021;53(6):1080-1091.
45. Kayanoki Y, Fujii J, Islam KN, et al. The protective role of glutathione peroxidase in apoptosis induced by reactive oxygen species. J Biochem. 1996;119(4):817-822.
46. Shisler JL, Senkevich TG, Berry MJ, et al. Ultraviolet-induced cell death blocked by a selenoprotein from a human dermatotropic poxvirus. Science. 1998;279(5347):102-105.
47. Bugert JJ. Molluscum contagiosum virus. In: Reference Module in Biomedical Sciences. New York: Elsevier; 2014.
48. Harvey IB, Wang X, Fremont DH. Molluscum contagiosum virus MC80 sabotages MHC-I antigen presentation by targeting tapasin for ER-associated degradation. PLoS Pathog. 2019;15(4):e1007711.
49. McFadden G. Poxvirus tropism. Nat Rev Microbiol. 2005;3(3):201-213.
50. Tilstra JS, Clauson CL, Niedernhofer LJ, Robbins PD. NF-κB in Aging and Disease. Aging Dis. 2011;2(6):449-465.
51. Ow YLP, Green DR, Hao Z, Mak TW. Cytochrome c: functions beyond respiration. Nat Rev Mol Cell Biol. 2008;9(7):532-542.
52. Browning JC, Enloe C, Cartwright M, et al. Efficacy and safety of topical nitric oxide-releasing berdazimer gel in patients with molluscum contagiosum: a phase 3 randomized clinical trial. JAMA Dermatol. Published online July 13, 2022. doi:10.1001/jamadermatol.2022.2721
53. Stasko N, McHale K, Hollenbach SJ, et al. nitric oxide-releasing macromolecule exhibits broad-spectrum antifungal activity and utility as a topical treatment for superficial fungal infections. Antimicrob Agents Chemother. 2018;62(7). doi:10.1128/AAC.01026-17
54. Tyring SK, Rosen T, Berman B, et al. A phase 2 controlled study of sb206, a topical nitric oxide-releasing drug for extragenital wart treatment. J Drugs Dermatol. 2018;17(10):1100-1105.
55. Guttman-Yassky E, Gallo RL, Pavel AB, et al. A nitric oxide-releasing topical medication as a potential treatment option for atopic dermatitis through antimicrobial and anti-inflammatory activity. J Invest Dermatol. 2020;140(12):2531-2535.e2.
56. Oza VS. Molluscum contagiosum therapeutics—new options may be around the corner. JAMA Dermatol. 2022;158(8):863-864.
57. Eichenfield LF, McFalda W, Brabec B, et al. Safety and efficacy of vp-102, a proprietary, drug-device combination product containing cantharidin, 0.7% (w/v), in children and adults with molluscum contagiosum: 2 phase 3 randomized clinical trials. JAMA Dermatol. 2020;156(12):1315-1323.
5. Centers for Disease Control and Prevention. Long term effects. Available at: https://www.cdc.gov/poxvirus/molluscum-contagiosum/long-term-effects. html. Accessed August 31, 2022.
6. Leung AKC, Barankin B, Hon KLE. Molluscum contagiosum: An update. Recent Pat Inflamm Allergy Drug Discov. 2017;11(1):22-31.
7. Chen X, Anstey AV, Bugert JJ. Molluscum contagiosum virus infection. Lancet Infect Dis. 2013;13(10):877-888.
8. Shisler JL. Immune evasion strategies of molluscum contagiosum virus. Adv Virus Res. 2015;92:201-252.
9. Na CH, Kim DJ, Kim MS, et al. Successful treatment of molluscum contagiosum with intralesional immunotherapy by measles, mumps, and rubella vaccine: a report of two cases. Dermatol Ther. 2014;27(6):373-376.
10. Smith KJ, Skelton H. Molluscum Contagiosum. Am J Clin Dermatol. 2002;3(8):535-545.
11. Biswas S, Smith GL, Roy EJ, et al. A comparison of the effect of molluscum contagiosum virus MC159 and MC160 proteins on vaccinia virus virulence in intranasal and intradermal infection routes. J Gen Virol. 2018;99(2):246-252.
12. Douglass NJ, Blake NW, Cream JJ, et al. Similarity in genome organization between molluscum contagiosum virus (MCV) and vaccinia virus (VV): identification of MCV homologues of the VV genes for protein kinase 2, structural protein VP8, RNA polymerase 35 kDa subunit and 3betahydroxysteroid dehydrogenase. J Gen Virol. 1996;77 ( Pt 12):3113-3120.
13. Brady G, Haas DA, Farrell PJ, et al. Molluscum contagiosum virus protein MC005 inhibits NF-κB activation by targeting NEMO-regulated IκB kinase activation. J Virol. 2017;91(15). doi:10.1128/JVI.00545-17
14. Bugert JJ, Darai G. Recent advances in molluscum contagiosum virus research. Arch Virol Suppl. 1997;13:35-47.
15. Senkevich TG, Koonin EV, Bugert JJ, et al. The genome of molluscum contagiosum virus: analysis and comparison with other poxviruses. Virology. 1997;233(1):19-42.
16. Maeda-Chubachi T, Hebert D, Messersmith E, et al. SB206, a nitric oxidereleasing topical medication, induces the beginning of the end sign and molluscum clearance. JID Innov. 2021;1(3):100019.
17. Olsen JR, Gallacher J, Finlay AY, et al. Time to resolution and effect on quality of life of molluscum contagiosum in children in the UK: a prospective community cohort study. Lancet Infect Dis. 2015;15(2):190-195.
18. Molluscum contagiosum: Diagnosis and treatment. Accessed August 31, 2022. https://www.aad.org/public/diseases/a-z/molluscum-contagiosumtreatment
19. Butala N, Siegfried E, Weissler A. Molluscum BOTE sign: a predictor of imminent resolution. Pediatrics. 2013;131(5):e1650-e1653.
20. Institute of Medicine (US) Committee on the Assessment of Future Scientific Needs for Live Variola Virus. Clinical Features of Smallpox. National Academies Press (US); 1999.
21. Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol. 2009;1(6):a001651.
22. Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2. doi:10.1038/sigtrans.2017.
23. Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol. 2014;5:461.
24. Lei V, Petty AJ, Atwater AR, et al. Skin viral infections: host antiviral innate immunity and viral immune evasion. Front Immunol. 2020;11:593901.
25. Hayden MS, Ghosh S. Regulation of NF-κB by TNF family cytokines. Semin Immunol. 2014;26(3):253-266.
26. Brady G, Haas DA, Farrell PJ, et al. Poxvirus protein mc132 from molluscum contagiosum virus inhibits nf-b activation by targeting p65 for degradation. J Virol. 2015;89(16):8406-8415.
27. Tran K, Merika M, Thanos D. Distinct functional properties of IkappaB alpha and IkappaB beta. Mol Cell Biol. 1997;17(9):5386-5399. 28. Nichols DB, Shisler JL. The MC160 protein expressed by the dermatotropic poxvirus molluscum contagiosum virus prevents tumor necrosis factor alpha-induced NF-kappaB activation via inhibition of I kappa kinase complex formation. J Virol. 2006;80(2):578-586.
29. Randall CMH, Jokela JA, Shisler JL. The MC159 protein from the molluscum contagiosum poxvirus inhibits NF-κB activation by interacting with the IκB kinase complex. J Immunol. 2012;188(5):2371-2379.
30. Biswas S, Shisler JL. Molluscum contagiosum virus MC159 abrogates cIAP1-NEMO interactions and inhibits NEMO polyubiquitination. J Virol. 2017;91(15). doi:10.1128/JVI.00276-17
31. Thurau M, Everett H, Tapernoux M, et al. The TRAF3-binding site of human molluscipox virus FLIP molecule MC159 is critical for its capacity to inhibit Fas-induced apoptosis. Cell Death Differ. 2006;13(9):1577-1585.
32. Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev. 2001;14(4):778-809.
33. Randall CMH, Biswas S, Selen CV, et al. Inhibition of interferon gene activation by death-effector domain-containing proteins from the molluscum contagiosum virus. Proc Natl Acad Sci U S A. 2014;111(2):E265-E272.
34. De Martini W, Coutu J, Bugert J, et al. The molluscum contagiosum virus protein MC163 inhibits TNF-α-induced NF-κB activation. Future Virol. 2019;14(5):319-333.
35. Seton Hall University. Characterization of Immune Evasion Properties of the Molluscum Contagiosum Virus MC163 Protein. Available at: https:// scholarship.shu.edu/dissertations/2704. Accessed August 22, 2022.
36. Coutu J, Ryerson MR, Bugert J, et al. The molluscum contagiosum virus protein MC163 localizes to the mitochondria and dampens mitochondrial mediated apoptotic responses. Virology. 2017;505:91-101.
37. Dinarello CA, Novick D, Kim S, et al. Interleukin-18 and IL-18 binding protein. Front Immunol. 2013;4:289.
38. Xiang Y, Moss B. IL-18 binding and inhibition of interferon γ induction by human poxvirus-encoded proteins. Proc Natl Acad Sci. 1999;96(20):11537- 11542.
39. Xiang Y, Moss B. Correspondence of the functional epitopes of poxvirus and human interleukin-18-binding proteins. J Virol. 2001;75(20):9947-9954.
40. Lüttichau HR, Gerstoft J, Schwartz TW. MC148 encoded by human molluscum contagiosum poxvirus is an antagonist for human but not murine CCR8. J Leukoc Biol. 2001;70(2):277-282.
41. Damon I, Murphy PM, Moss B. Broad spectrum chemokine antagonistic activity of a human poxvirus chemokine homolog. Proc Natl Acad Sci U S A. 1998;95(11):6403-6407.
42. Mohr S, Grandemange S, Massimi P, et al. Targeting the retinoblastoma protein by MC007L, gene product of the molluscum contagiosum virus: detection of a novel virus-cell interaction by a member of the poxviruses. J Virol. 2008;82(21):10625-10633.
43. Ahlander J, Bosco G. The RB/E2F pathway and regulation of RNA processing. Biochem Biophys Res Commun. 2009;384(3):280-283. 44. Lee S, Lee EK, Kang DH, et al. Glutathione peroxidase-1 regulates ASK1- dependent apoptosis via interaction with TRAF2 in RIPK3-negative cancer cells. Exp Mol Med. 2021;53(6):1080-1091.
45. Kayanoki Y, Fujii J, Islam KN, et al. The protective role of glutathione peroxidase in apoptosis induced by reactive oxygen species. J Biochem. 1996;119(4):817-822.
46. Shisler JL, Senkevich TG, Berry MJ, et al. Ultraviolet-induced cell death blocked by a selenoprotein from a human dermatotropic poxvirus. Science. 1998;279(5347):102-105.
47. Bugert JJ. Molluscum contagiosum virus. In: Reference Module in Biomedical Sciences. New York: Elsevier; 2014.
48. Harvey IB, Wang X, Fremont DH. Molluscum contagiosum virus MC80 sabotages MHC-I antigen presentation by targeting tapasin for ER-associated degradation. PLoS Pathog. 2019;15(4):e1007711.
49. McFadden G. Poxvirus tropism. Nat Rev Microbiol. 2005;3(3):201-213.
50. Tilstra JS, Clauson CL, Niedernhofer LJ, Robbins PD. NF-κB in Aging and Disease. Aging Dis. 2011;2(6):449-465.
51. Ow YLP, Green DR, Hao Z, Mak TW. Cytochrome c: functions beyond respiration. Nat Rev Mol Cell Biol. 2008;9(7):532-542.
52. Browning JC, Enloe C, Cartwright M, et al. Efficacy and safety of topical nitric oxide-releasing berdazimer gel in patients with molluscum contagiosum: a phase 3 randomized clinical trial. JAMA Dermatol. Published online July 13, 2022. doi:10.1001/jamadermatol.2022.2721
53. Stasko N, McHale K, Hollenbach SJ, et al. nitric oxide-releasing macromolecule exhibits broad-spectrum antifungal activity and utility as a topical treatment for superficial fungal infections. Antimicrob Agents Chemother. 2018;62(7). doi:10.1128/AAC.01026-17
54. Tyring SK, Rosen T, Berman B, et al. A phase 2 controlled study of sb206, a topical nitric oxide-releasing drug for extragenital wart treatment. J Drugs Dermatol. 2018;17(10):1100-1105.
55. Guttman-Yassky E, Gallo RL, Pavel AB, et al. A nitric oxide-releasing topical medication as a potential treatment option for atopic dermatitis through antimicrobial and anti-inflammatory activity. J Invest Dermatol. 2020;140(12):2531-2535.e2.
56. Oza VS. Molluscum contagiosum therapeutics—new options may be around the corner. JAMA Dermatol. 2022;158(8):863-864.
57. Eichenfield LF, McFalda W, Brabec B, et al. Safety and efficacy of vp-102, a proprietary, drug-device combination product containing cantharidin, 0.7% (w/v), in children and adults with molluscum contagiosum: 2 phase 3 randomized clinical trials. JAMA Dermatol. 2020;156(12):1315-1323.
AUTHOR CORRESPONDENCE
Brian Berman MD PhD bbmdphd@gmail.com
