Temporal and spatial characterization of keratinocytes supporting orf virus replication
Reflecting their tropism for keratinocytes, most poxviruses that infect vertebrates replicate to high titers and cause pathology in the skin. Keratinocytes, the main cells of the epidermis, are found in different stages of a differentiation program that produces the critical barrier against environm...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1486778/full |
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| author | Byung-Joon Seung Sushil Khatiwada Daniel L. Rock Gustavo Delhon |
| author_facet | Byung-Joon Seung Sushil Khatiwada Daniel L. Rock Gustavo Delhon |
| author_sort | Byung-Joon Seung |
| collection | DOAJ |
| description | Reflecting their tropism for keratinocytes, most poxviruses that infect vertebrates replicate to high titers and cause pathology in the skin. Keratinocytes, the main cells of the epidermis, are found in different stages of a differentiation program that produces the critical barrier against environmental damage. While systemic poxviruses (e.g. smallpox virus, sheeppox virus) also infect other cell types, the parapoxvirus orf virus (ORFV), which causes localized infections in sheep and goats, has not been shown to replicate in cells other than keratinocytes. Notably, ORFV infection only occurs after or concomitant with epidermal damage and the subsequent healing response and shows unexplained delayed virus replication in an uncharacterized keratinocyte subpopulation. Using in situ hybridization, immunohistochemistry, confocal microscopy, qPCR, and a full-thickness wound/infection model in sheep, the natural host, we show that during an initial 2-day eclipse phase viral transcription and viral DNA replication are not detected. Between days 2 and 3 pi, viral transcription is first detected in keratinocytes of the stratum granulosum and upper stratum spinosum in the proliferative zone at the wound margin. These cells are positive for cytokeratin 10, a suprabasal marker; cytokeratin 6, a protein induced during early repair responses; stratum granulosum markers filaggrin and loricrin; and negative for the nuclear proliferation marker Ki-67 and cytokeratin 14, a basal cell marker. This marker profile suggests that keratinocytes supportive of viral replication are engaged in advanced keratinocyte differentiation rather than proliferation. |
| format | Article |
| id | doaj-art-38728bb9e8c445708f0128ebf9def7a2 |
| institution | Kabale University |
| issn | 2235-2988 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-38728bb9e8c445708f0128ebf9def7a22025-01-31T06:39:53ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-01-011410.3389/fcimb.2024.14867781486778Temporal and spatial characterization of keratinocytes supporting orf virus replicationByung-Joon Seung0Sushil Khatiwada1Daniel L. Rock2Gustavo Delhon3Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesDepartment of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesDepartment of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesSchool of Veterinary Medicine and Biomedical Sciences, and Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE, United StatesReflecting their tropism for keratinocytes, most poxviruses that infect vertebrates replicate to high titers and cause pathology in the skin. Keratinocytes, the main cells of the epidermis, are found in different stages of a differentiation program that produces the critical barrier against environmental damage. While systemic poxviruses (e.g. smallpox virus, sheeppox virus) also infect other cell types, the parapoxvirus orf virus (ORFV), which causes localized infections in sheep and goats, has not been shown to replicate in cells other than keratinocytes. Notably, ORFV infection only occurs after or concomitant with epidermal damage and the subsequent healing response and shows unexplained delayed virus replication in an uncharacterized keratinocyte subpopulation. Using in situ hybridization, immunohistochemistry, confocal microscopy, qPCR, and a full-thickness wound/infection model in sheep, the natural host, we show that during an initial 2-day eclipse phase viral transcription and viral DNA replication are not detected. Between days 2 and 3 pi, viral transcription is first detected in keratinocytes of the stratum granulosum and upper stratum spinosum in the proliferative zone at the wound margin. These cells are positive for cytokeratin 10, a suprabasal marker; cytokeratin 6, a protein induced during early repair responses; stratum granulosum markers filaggrin and loricrin; and negative for the nuclear proliferation marker Ki-67 and cytokeratin 14, a basal cell marker. This marker profile suggests that keratinocytes supportive of viral replication are engaged in advanced keratinocyte differentiation rather than proliferation.https://www.frontiersin.org/articles/10.3389/fcimb.2024.1486778/fullorf viruspathogenesiskeratinocytesfull thickness wound skin modelsheepin situ hybridization (ISH) |
| spellingShingle | Byung-Joon Seung Sushil Khatiwada Daniel L. Rock Gustavo Delhon Temporal and spatial characterization of keratinocytes supporting orf virus replication Frontiers in Cellular and Infection Microbiology orf virus pathogenesis keratinocytes full thickness wound skin model sheep in situ hybridization (ISH) |
| title | Temporal and spatial characterization of keratinocytes supporting orf virus replication |
| title_full | Temporal and spatial characterization of keratinocytes supporting orf virus replication |
| title_fullStr | Temporal and spatial characterization of keratinocytes supporting orf virus replication |
| title_full_unstemmed | Temporal and spatial characterization of keratinocytes supporting orf virus replication |
| title_short | Temporal and spatial characterization of keratinocytes supporting orf virus replication |
| title_sort | temporal and spatial characterization of keratinocytes supporting orf virus replication |
| topic | orf virus pathogenesis keratinocytes full thickness wound skin model sheep in situ hybridization (ISH) |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1486778/full |
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