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Although eradication of the notorious smallpox has been a globally successful healthcare phenomenon, the recent emergence of Monkeypox virus, also belonging to the Orthopoxvirus genus and causing human disease, albeit milder than smallpox, is a cause of significant public health concern. The ongoing outbreak of monkeypox, demonstrating human\u2013human transmission, in previously nonendemic countries, calls for critical need into further research in the areas of viral biology, ecology, and epidemiology to better understand, prevent and treat human infections. In the wake of these recent events, it becomes important to revisit poxviral infections, their pathogenesis and ability to cause infection across multiple nonhuman hosts and leap to a human host. The poxviruses that cause human diseases include Monkeypox virus, Molluscum contagiosum virus, and Orf virus. In this review, we summarize the current understanding of various poxviruses causing human diseases, provide insights into their replication and pathogenicity, disease progression and symptoms, preventive and treatment options, and their importance in shaping modern medicine through application in gene therapy, oncolytic viral therapies for human cancers, or as poxvirus vectors for vaccines.<\/jats:p>","DOI":"10.1177\/20499361221136751","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T04:57:57Z","timestamp":1668401877000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Poxvirus-driven human diseases and emerging therapeutics"],"prefix":"10.1177","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2877-3542","authenticated-orcid":false,"given":"Kritika","family":"Srinivasan Rajsri","sequence":"first","affiliation":[{"name":"Division of Biomaterials, Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY, USA"},{"name":"Department of Pathology, Vilcek Institute, New York University School of Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2516-2079","authenticated-orcid":false,"given":"Mana","family":"Rao","sequence":"additional","affiliation":[{"name":"Essen Medical Associates, Bronx, NY 10461, USA. 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