Next Article in Journal
Molecular Detection and Characterization of Borrelia garinii (Spirochaetales: Borreliaceae) in Ixodes nipponensis (Ixodida: Ixodidae) Parasitizing a Dog in Korea
Next Article in Special Issue
HPV Oncoproteins and the Ubiquitin Proteasome System: A Signature of Malignancy?
Previous Article in Journal
The Impact of SsPI-1 Deletion on Streptococcus suis Virulence
Previous Article in Special Issue
β-HPV 8E6 Attenuates ATM and ATR Signaling in Response to UV Damage
Open AccessArticle

Surfactant Protein A Impairs Genital HPV16 Pseudovirus Infection by Innate Immune Cell Activation in A Murine Model

1
Division of Medical Biochemistry and Structural Biology, Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town 7925, South Africa
2
Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa
3
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town 7925, South Africa
4
Institute of Microbiology and Infection, University of Birmingham, Birmingham B15 2TT, UK
5
Institute for Women’s Health, University College London, London WC1E 6BT, UK
6
Child Health, Division of Clinical and Experimental Sciences, Department of Child Health, University of Southampton, Southampton SO17 1BJ, UK
7
National Heart & Lung Institute, Imperial College London, London SW7 2AZ, UK
8
SAMRC/UCT Gynaecological Cancer Research Centre (GCRC), Cape Town 7925, South Africa
*
Author to whom correspondence should be addressed.
Both authors contributed equally to this study.
Pathogens 2019, 8(4), 288; https://doi.org/10.3390/pathogens8040288
Received: 11 November 2019 / Revised: 3 December 2019 / Accepted: 4 December 2019 / Published: 6 December 2019
Infection by oncogenic human papillomavirus (HPV) is the principle cause of cervical cancer and other anogenital cancers. The majority of cervical cancer cases occur in low- and middle-income countries (LMIC). Prophylactic vaccines exist to combat HPV infection but accessibility to these in LMIC is limited. Alternative preventative measures against HPV infection are therefore also needed to control cervical cancer risk. HPV employs multiple mechanisms to evade the host immune response. Therefore, an approach to promote HPV recognition by the immune system can reduce infection. Surfactant proteins A and D (SP-A and SP-D) are highly effective innate opsonins of pathogens. Their function is primarily understood in the lung, but they are also expressed at other sites of the body, including the female reproductive tract (FRT). We hypothesized that raised levels of SP-A and/or SP-D may enhance immune recognition of HPV and reduce infection. Co-immunoprecipitation and flow cytometry experiments showed that purified human SP-A protein directly bound HPV16 pseudovirions (HPV16-PsVs), and the resulting HPV16-PsVs/SP-A complex enhanced uptake of HPV16-PsVs by RAW264.7 murine macrophages. In contrast, a recombinant fragment of human SP-D bound HPV16-PsVs weakly and had no effect on viral uptake. To assess if SP-A modulates HPV16-PsVs infection in vivo, a murine cervicovaginal challenge model was applied. Surprisingly, neither naïve nor C57BL/6 mice challenged with HPV16-PsVs expressed SP-A in the FRT. However, pre-incubation of HPV16-PsVs with purified human SP-A at a 1:10 (w/w) ratio significantly reduced the level of HPV16-PsV infection. When isolated cells from FRTs of naïve C57BL/6 mice were incubated with HPV16-PsVs and stained for selected innate immune cell populations by flow cytometry, significant increases in HPV16-PsVs uptake by eosinophils, neutrophils, monocytes, and macrophages were observed over time using SP-A-pre-adsorbed virions compared to control particles. This study is the first to describe a biochemical and functional association of HPV16 virions with the innate immune molecule SP-A. We show that SP-A impairs HPV16-PsVs infection and propose that SP-A is a potential candidate for use in topical microbicides which provide protection against new HPV infections. View Full-Text
Keywords: human papillomavirus (HPV); surfactant proteins A and D (SP-A and SP-D); murine cervicovaginal challenge model; innate immune cells; opsonins human papillomavirus (HPV); surfactant proteins A and D (SP-A and SP-D); murine cervicovaginal challenge model; innate immune cells; opsonins
Show Figures

Figure 1

MDPI and ACS Style

Ujma, S.; Carse, S.; Chetty, A.; Horsnell, W.; Clark, H.; Madsen, J.; Mackay, R.-M.; Watson, A.; Griffiths, M.; Katz, A.A.; Schäfer, G. Surfactant Protein A Impairs Genital HPV16 Pseudovirus Infection by Innate Immune Cell Activation in A Murine Model. Pathogens 2019, 8, 288.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop