Title: | Functional characterisation of surfactant protein A as a novel prophylactic means against oncogenic HPV infections |
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Authors: | ID Carse, Sinead (Author) ID Reid, Tim (Author) ID Madsen, Jens (Author) ID Clark, Howard (Author) ID Kirjakulov, Artur (Author) ID Bergant Marušič, Martina (Author) ID Schäfer, Georgia (Author) |
Files: | https://www.mdpi.com/1422-0067/25/14/7712
ijms-25-07712-published2024Sinead.pdf (6,10 MB) MD5: 8A0D589A3E3A66D6742CA96470700FF1
https://www.mdpi.com/1422-0067/25/14/7712/pdf
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Language: | English |
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Work type: | Unknown |
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Typology: | 1.01 - Original Scientific Article |
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Organization: | UNG - University of Nova Gorica
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Abstract: | Human papillomavirus (HPV) infection poses a significant health challenge, particularly in low- and middle-income countries (LMIC), where limited healthcare access and awareness hinder vaccine accessibility. To identify alternative HPV targeting interventions, we previously reported on surfactant protein A (SP-A) as a novel molecule capable of recognising HPV16 pseudovirions (HPV16-PsVs) and reducing infection in a murine cervicovaginal HPV challenge model. Building on these findings, our current study aimed to assess SP-A’s suitability as a broad-spectrum HPV-targeting molecule and its impact on innate immune responses. We demonstrate SP-A’s ability to agglutinate and opsonise multiple oncogenic HPV-PsVs types, enhancing their uptake and clearance by RAW264.7 murine macrophages and THP-1 human-derived immune cells. The SP-A opsonisation of HPV not only led to increased lysosomal accumulation in macrophages and HaCaT keratinocytes but also resulted in a decreased infection of HaCaT cells, which was further decreased when co-cultured with innate immune cells. An analysis of human innate immune cell cytokine profiles revealed a significant inflammatory response upon SP-A exposure, potentially contributing to the overall inhibition of HPV infection. These results highlight the multi-layered impact of SP-A on HPV, innate immune cells and keratinocytes and lay the basis for the development of alternative prophylactic interventions against diverse HPV types. |
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Keywords: | surfactant protein A, SP-A, human papillomavirus, HPV, pseudovirus, cervical cancer, HPV prophylactic, low- and middle-income countries, LMIC |
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Publication status: | Published |
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Publication version: | Version of Record |
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Publication date: | 01.01.2024 |
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Year of publishing: | 2024 |
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Number of pages: | str. 1-22 |
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Numbering: | Vol. 25, issue 14, [article no.] 7712 |
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PID: | 20.500.12556/RUNG-9196 |
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COBISS.SI-ID: | 202458371 |
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UDC: | 54 |
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ISSN on article: | 1422-0067 |
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eISSN: | 1422-0067 |
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DOI: | 10.3390/ijms25147712 |
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NUK URN: | URN:SI:UNG:REP:Y1ZZ8AGC |
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Publication date in RUNG: | 22.07.2024 |
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Views: | 841 |
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Downloads: | 7 |
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