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Functional characterisation of surfactant protein A as a novel prophylactic means against oncogenic HPV infectionsSinead Carse,
Tim Reid,
Jens Madsen,
Howard Clark,
Artur Kirjakulov,
Martina Bergant Marušič,
Georgia Schäfer, 2024, original scientific article
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.
Keywords: surfactant protein A, SP-A, human papillomavirus, HPV, pseudovirus, cervical cancer, HPV prophylactic, low- and middle-income countries, LMIC
Published in RUNG: 22.07.2024; Views: 167; Downloads: 3
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