Effects of ganciclovir treatment in a murine model of cytomegalovirus-induced hearing loss.

Autor: Haller TJ; Division of Otolaryngology-Head and Neck Surgery, University of Utah School of Medicine, Salt Lake City, Utah, U.S.A., Price MS; School of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, U.S.A., Lindsay SR; Division of Otolaryngology-Head and Neck Surgery, University of Utah School of Medicine, Salt Lake City, Utah, U.S.A., Hillas E; Department of Surgery, University of Utah, Salt Lake City, Utah, U.S.A., Seipp M; Department of Surgery, University of Utah, Salt Lake City, Utah, U.S.A., Firpo MA; Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah, U.S.A., Park AH; Division of Otolaryngology-Head and Neck Surgery, University of Utah School of Medicine, Salt Lake City, Utah, U.S.A.
Jazyk: angličtina
Zdroj: The Laryngoscope [Laryngoscope] 2020 Apr; Vol. 130 (4), pp. 1064-1069. Date of Electronic Publication: 2019 Jun 11.
DOI: 10.1002/lary.28134
Abstrakt: Objective: To determine whether ganciclovir (GCV) treatment reduces sensorineural hearing loss in cytomegalovirus (CMV)-infected mice. The effects of GCV on viral load, absolute neutrophil count (ANC), and outer hair cell (OHC) integrity were also investigated.
Methods: Infected BALB/c mice were inoculated with murine CMV on postnatal day 3. Those treated with GCV received an intraperitoneal injection twice a day for 14 days. Auditory thresholds were assessed using distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) testing 4 weeks after inoculation. Temporal bones were used for determination of viral load by quantitative polymerase chain reaction and hair cell quantification by scanning electron microscopy. ANCs were completed by an automated hematology analyzer, with manual review for confirmation.
Results: GCV-treated CMV-infected mice had lower ABR (P < 0.0001, Kruskal-Wallis test) and DPOAE (P < 0.0001) thresholds compared to CMV-infected untreated mice, indicating that GCV protected mice from CMV-induced hearing loss. Viral load in infected populations undergoing GCV treatment was significantly decreased (P = 0.03) relative to untreated mice. GCV treatment alone had no effect on ABR and DPOAE compared to untreated, uninfected controls (P = 0.1, P = 0.24, respectively). GCV-treated mice received increased protection from OHC loss when compared to untreated groups, with total OHC losses of approximately 7% and 14%, respectively (P < 0.05). Neutropenia was absent after 7 days of GCV treatment.
Conclusion: Ganciclovir effectively ameliorated SNHL and partially protected from OHC loss in a preclinical model of congenital CMV infection, seemingly by reducing viral load.
Level of Evidence: NA Laryngoscope, 130:1064-1069, 2020.
(© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)
Databáze: MEDLINE
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