The use of a topical protease inhibitor, Saquinavir, to alleviate mouse papillomavirus-mediated anal disease

Laura C Gunder¹, Hillary R Johnson², Heather A Green³, Andrea Bilger⁴, Tyra H Moyer⁵, Wei Zhang⁶, Marissa R Ziolkowski⁷, Payton A Bertrang⁸, Evie H Carchman⁹

Affiliations

¹ Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53792, USA. Electronic address: gunderl@surgery.wisc.edu.
² Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53792, USA. Electronic address: hjohnson42@wisc.edu.
³ University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53705, USA. Electronic address: hagreen@uwcarbone.wisc.edu.
⁴ McArdle Laboratory for Cancer Research, Department of Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Wisconsin Institutes for Medical Research, 1111 Highland Ave, Madison, WI, 53705, USA. Electronic address: bilger@oncology.wisc.edu.
⁵ Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53792, USA. Electronic address: tmoyer2@wisc.edu.
⁶ Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, 3170 UW Medical Foundation Centennial Building (MFCB),1685 Highland Avenue, Madison, WI, 53705, USA. Electronic address: wzhang566@wisc.edu.
⁷ Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53792, USA. Electronic address: mziolkowski@wisc.edu.
⁸ Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53792, USA. Electronic address: pbertrang@wisc.edu.
⁹ Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53792, USA; University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53705, USA; William S. Middleton Memorial Veterans Hospital, 2500 Overlook Terrace, Madison, WI, 53705, USA. Electronic address: carchman@surgery.wisc.edu.

PMID: 36206607
DOI: 10.1016/j.virol.2022.09.012

Free article

The use of a topical protease inhibitor, Saquinavir, to alleviate mouse papillomavirus-mediated anal disease

Laura C Gunder et al. Virology. 2022 Nov.

Free article

. 2022 Nov:576:96-104.

doi: 10.1016/j.virol.2022.09.012. Epub 2022 Sep 29.

Authors

Laura C Gunder¹, Hillary R Johnson², Heather A Green³, Andrea Bilger⁴, Tyra H Moyer⁵, Wei Zhang⁶, Marissa R Ziolkowski⁷, Payton A Bertrang⁸, Evie H Carchman⁹

Affiliations

¹ Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53792, USA. Electronic address: gunderl@surgery.wisc.edu.
² Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53792, USA. Electronic address: hjohnson42@wisc.edu.
³ University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53705, USA. Electronic address: hagreen@uwcarbone.wisc.edu.
⁴ McArdle Laboratory for Cancer Research, Department of Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Wisconsin Institutes for Medical Research, 1111 Highland Ave, Madison, WI, 53705, USA. Electronic address: bilger@oncology.wisc.edu.
⁵ Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53792, USA. Electronic address: tmoyer2@wisc.edu.
⁶ Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, 3170 UW Medical Foundation Centennial Building (MFCB),1685 Highland Avenue, Madison, WI, 53705, USA. Electronic address: wzhang566@wisc.edu.
⁷ Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53792, USA. Electronic address: mziolkowski@wisc.edu.
⁸ Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53792, USA. Electronic address: pbertrang@wisc.edu.
⁹ Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53792, USA; University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53705, USA; William S. Middleton Memorial Veterans Hospital, 2500 Overlook Terrace, Madison, WI, 53705, USA. Electronic address: carchman@surgery.wisc.edu.

PMID: 36206607
DOI: 10.1016/j.virol.2022.09.012

Abstract

Select protease inhibitors (PI) have been found to be effective in decreasing human papillomavirus oncoprotein expression. This study evaluated whether the topical PI, Saquinavir (SQV), promotes viral clearance in an infectious mouse model with Mus musculus papillomavirus 1 (MmuPV1). NOD scid gamma (NSG) mice were anally infected with ∼4 × 10⁸ viral genome equivalents of MmuPV1 and 120 days post-infection (when majority have high-grade anal dysplasia), began topical treatments: control (mock), 7,12-dimethylbenz(a)anthracene (DMBA) only, once weekly to promote carcinogenesis, 1% SQV only, daily (Monday - Friday), and SQV + DMBA. Viral MmuPV1 load was analyzed from anal lavages pre and post-treatment. Anal tissue was harvested, processed, and evaluated for drug absorption, grade of anal disease, and anal viral RNA. Results suggest that topical SQV promotes decreased viral shedding in female mice treated with SQV.

Keywords: Anal cancer; Anal dysplasia; Mouse papillomavirus; Protease inhibitors; Squamous cell carcinoma; Viral clearance.

Published by Elsevier Inc.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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The use of a topical protease inhibitor, Saquinavir, to alleviate mouse papillomavirus-mediated anal disease

Affiliations

The use of a topical protease inhibitor, Saquinavir, to alleviate mouse papillomavirus-mediated anal disease

Authors

Affiliations

Abstract

Conflict of interest statement

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous