Human Nasal Turbinate Tissues in Organ Culture as a Model for Human Cytomegalovirus Infection at the Mucosal Entry Site
| Autor: | Menachem Oberbaum, Shay Tayeb, Yiska Weisblum, John A. Ives, Michael Drendel, Ophir Ilan, Michael Wolf, Wayne B. Jonas, Yuval Nevo, Dana G. Wolf, Karen Meir, Sharona Elgavish, Zichria Zakay-Rones, Ido From, Arkadi Yakirevitch, Menachem Gross, Amos Panet, Or Alfi |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Human cytomegalovirus Stromal cell viruses Foreskin Immunology Cellular Response to Infection Cytomegalovirus Mucous membrane of nose Biology Turbinates Organ culture Microbiology Cell Line Organ Culture Techniques Pregnancy Viral entry Virology medicine Humans Pathogen Nasal Turbinate Mucous Membrane Innate immune system Endothelial Cells Fibroblasts Virus Internalization medicine.disease Immunity Innate Infectious Disease Transmission Vertical Insect Science Cytomegalovirus Infections Female |
| Zdroj: | J Virol |
| ISSN: | 1098-5514 0022-538X |
| Popis: | The initial events of viral infection at the primary mucosal entry site following horizontal person-to-person transmission have remained ill defined. Our limited understanding is further underscored by the absence of animal models in the case of human-restricted viruses, such as human cytomegalovirus (HCMV), a leading cause of congenital infection and a major pathogen in immunocompromised individuals. Here, we established a novel ex vivo model of HCMV infection in native human nasal turbinate tissues. Nasal turbinate tissue viability and physiological functionality were preserved for at least 7 days in culture. We found that nasal mucosal tissues were susceptible to HCMV infection, with predominant infection of ciliated respiratory epithelial cells. A limited viral spread was demonstrated, involving mainly stromal and vascular endothelial cells within the tissue. Importantly, functional antiviral and proleukocyte chemotactic signaling pathways were significantly upregulated in the nasal mucosa in response to infection. Conversely, HCMV downregulated the expression of nasal epithelial cell-related genes. We further revealed tissue-specific innate immune response patterns to HCMV, comparing infected human nasal mucosal and placental tissues, representing the viral entry and the maternal-to-fetal transmission sites, respectively. Taken together, our studies provide insights into the earliest stages of HCMV infection. Studies in this model could help evaluate new interventions against the horizontal transmission of HCMV. IMPORTANCE HCMV is a ubiquitous human pathogen causing neurodevelopmental disabilities in congenitally infected children and severe disease in immunocompromised patients. The earliest stages of HCMV infection in the human host have remained elusive in the absence of a model for the viral entry site. Here, we describe the establishment and use of a novel nasal turbinate organ culture to study the initial steps of viral infection and the consequent innate immune responses within the natural complexity and the full cellular repertoire of human nasal mucosal tissues. This model can be applied to examine new antiviral interventions against the horizontal transmission of HCMV and potentially that of other viruses. |
| Databáze: | OpenAIRE |
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