The Larynx is Protected from Secondary and Vertical Papillomavirus Infection in Immunocompetent Mice

• Published in: The Laryngoscope 2024-05, Vol.134 (5), p.2322-2330
• Main Authors: King, Renee E., Rademacher, Josef, Ward‐Shaw, Ella T., Hu, Rong, Bilger, Andrea, Blaine‐Sauer, Simon, Spurgeon, Megan E., Thibeault, Susan L., Lambert, Paul F.
• Format: Article
• Language: English
• Subjects: animal model; Histopathology; Immunocompetence; Infections; Larynx; papillomavirus; viral transmission
• ISSN: 0023-852X; 1531-4995
• DOI: 10.1002/lary.31228

Objective Mouse papillomavirus MmuPV1 causes both primary and secondary infections of the larynx in immunocompromised mice. Understanding lateral and vertical transmission of papillomavirus to the larynx would benefit patients with recurrent respiratory papillomatosis (RRP). To test the hypothesis that the larynx is uniquely vulnerable to papillomavirus infection, and to further develop a mouse model of RRP, we assessed whether immunocompetent mice were vulnerable to secondary or vertical laryngeal infection with MmuPV1. Methods Larynges were collected from 405 immunocompetent adult mice that were infected with MmuPV1 in the oropharynx, oral cavity, or anus, and 31 mouse pups born to immunocompetent females infected in the cervicovaginal tract. Larynges were analyzed via polymerase chain reaction (PCR) of lavage fluid or whole tissues for viral DNA, histopathology, and/or in situ hybridization for MmuPV1 transcripts. Results Despite some positive laryngeal lavage PCR screens, all laryngeal tissue PCR and histopathology results were negative for MmuPV1 DNA, transcripts, and disease. There was no evidence for lateral spread of MmuPV1 to the larynges of immunocompetent mice that were infected in the oral cavity, oropharynx, or anus. Pups born to infected mothers were negative for laryngeal MmuPV1 infection from birth through weaning age. Conclusion Secondary and vertical laryngeal MmuPV1 infections were not found in immunocompetent mice. Further work is necessary to explore immunologic control of laryngeal papillomavirus infection in a mouse model and to improve preclinical models of RRP. Level of Evidence NA Laryngoscope, 134:2322–2330, 2024 In humans, human papillomaviruses that cause recurrent respiratory papillomatosis can spread to the larynx from other tissue sites (secondary infection), and to the larynx of infants from genitally infected mothers (vertical infection). We examined larynges of over 430 immunocompetent adult and juvenile mice infected with mouse papillomavirus MmuPV1 in tissues other than the larynx or born to infected mothers, respectively, and found no evidence of secondary or vertical laryngeal MmuPV1 infection. These results have clinically important implications regarding laryngeal vulnerability to HPV infection.