Effects of ganciclovir treatment in a murine model of cytomegalovirus‐induced hearing loss
Travis J. Haller BS Melissa S. Price BS Spencer R. Lindsay MPA Elaine Hillas MS Michael Seipp MS Matthew A. Firpo PhD Albert H. Park MD
First published: 11 June 2019 https://doi.org/10.1002/lary.28134
Editor's Note: This Manuscript was accepted for publication on May 28, 2019.
Presented as an oral presentation to Triological Society 122nd Annual Meeting at COSM, Austin, Texas, U.S.A., May 3.
This work was supported by a University of Utah Division of Otolaryngology–HNS research fund. The authors have no other funding, financial relationships, or conflicts of interest to disclose.
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Abstract
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, 2019
Travis J. Haller BS Melissa S. Price BS Spencer R. Lindsay MPA Elaine Hillas MS Michael Seipp MS Matthew A. Firpo PhD Albert H. Park MD
First published: 11 June 2019 https://doi.org/10.1002/lary.28134
Editor's Note: This Manuscript was accepted for publication on May 28, 2019.
Presented as an oral presentation to Triological Society 122nd Annual Meeting at COSM, Austin, Texas, U.S.A., May 3.
This work was supported by a University of Utah Division of Otolaryngology–HNS research fund. The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Read the full text
ePDFPDFTOOLS SHARE
Abstract
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, 2019
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