Virus infection is one of the most common etiologies of hearing loss. Hearing loss associated with viral infection can be unilateral or bilateral, mild or severe, sudden or progressive, and permanent or recoverable. Many viruses cause hearing loss in adults and children; however, the pathogenesis of hearing loss caused by viral infection is not fully understood. This review describes cytomegalovirus, the most common virus causing hearing loss, and other reported hearing loss-related viruses. We hope to provide a detailed description of pathogenic characteristics and research progress on pathology, hearing phenotypes, possible associated mechanisms, treatment, and prevention measures. This review aims to provide diagnostic and treatment assistance to clinical workers.

The connexin gene family is the most prevalent gene that contributes to hearing loss. Connexins 26 and 30, encoded by GJB2 and GJB6, respectively, are the most abundantly expressed connexins in the inner ear. Connexin 43, which is encoded by GJA1, appears to be widely expressed in various organs, including the heart, skin, the brain, and the inner ear. The mutations that arise in GJB2, GJB6, and GJA1 can all result in comprehensive or non-comprehensive genetic deafness in newborns. As it is predicted that connexins include at least 20 isoforms in humans, the biosynthesis, structural composition, and degradation of connexins must be precisely regulated so that the gap junctions can properly operate. Certain mutations result in connexins possessing a faulty subcellular localization, failing to transport to the cell membrane and preventing gap junction formation, ultimately leading to connexin dysfunction and hearing loss. In this review, we provide a discussion of the transport models for connexin 43, connexins 30 and 26, mutations affecting trafficking pathways of these connexins, the existing controversies in the trafficking pathways of connexins, and the molecules involved in connexin trafficking and their functions. This review can contribute to a new way of understanding the etiological principles of connexin mutations and finding therapeutic strategies for hereditary deafness.

Background: This study aimed to describe the distribution of the genotype and allele frequencies of GJB2 variants in the Chinese population of the Dongfeng Tongji cohort and to analyze the features of the hearing phenotype. Methods: We used data from 9910 participants in the Dongfeng Tongji cohort in 2013 and selected nine GJB2 variants. Pure tone audiometry was employed to measure hearing. Differences in genotype and allele frequencies were analyzed via chi-squared test or Fisher’s exact test. Results: Of the 9910 participants, 5742 had hearing loss. The genotype frequency of the GJB2 variant c.109G>A was statistically significantly distributed between the normal and impaired hearing groups, but not for the variant c.235delC. A higher frequency of the c.109G>A homozygous genotype was found in the hearing loss group (0.5%) than in the normal hearing group (0.1%). Patients with c.109G>A and c.235delC homozygous mutations exhibited varying degrees of hearing loss, mainly presenting sloping and flat audiogram shapes. Conclusions: A significant difference was found in the genotype frequency of the GJB2 variant c.109G>A between the case and control groups, but not in that of the variant c.235delC. Different degrees of hearing loss and various audiogram shapes were observed in patients with c.109G>A and c.235delC homozygous mutations.

Herpesvirus is a prevalent pathogen that primarily infects human epithelial cells and has the ability to reside in neurons. In the field of otolaryngology, herpesvirus infection primarily leads to hearing loss and vestibular neuritis and is considered the primary hypothesis regarding the pathogenesis of vestibular neuritis. In this review, we provide a summary of the effects of the herpes virus on cellular processes in both host cells and immune cells, with a focus on HSV-1 as illustrative examples.

To improve the etiological diagnosis of congenital hearing loss by combining whole-exome sequencing (WES) with cytomegalovirus (CMV) testing and to explore the potential benefits of adding CMV screening to newborn hearing screening, 80 children under 2 years of age with bilateral sensorineural hearing loss were recruited. Peripheral venous blood was extracted from the children for WES analysis. Saliva after mouthwash and the first urine in the morning were collected and used as samples to quantify CMV DNA copy number in urine and saliva by qPCR; among the 80 children with congenital deafness, 59 (74%) were found to have genetic variants that may cause congenital deafness, including 44 with GJB2 or SLC26A4 gene variant, 1 with STRC gene variant, and 14 with other genetic variants. A total of 12 children carried deafness gene variants associated with a syndrome; CMV test results showed that in two children, the CMV DNA copy number in saliva was >1000/mL, which indicates that they were CMV-positive, and their genetic test results were negative. A neonatal CMV test combined with genetic screening can improve the etiological diagnosis rate of congenital deafness, and the direct evidence of neonatal CMV infection deserves further verification.

Cytomegalovirus infection contributes to 10–30% of congenital hearing loss in children. Vertebrate peripheral auditory organs include the outer, middle, and inner ear. Their development is regulated by multiple signaling pathways. However, most ear diseases due to viral infections are due to congenital infections and reactivation and affect healthy adults to a lesser extent. This may be due to the fact that viral infections affect signaling pathways that are important for the development of peripheral hearing organs. Therefore, an in-depth understanding of the relationship between viral infections and the signaling pathways involved in the development of peripheral hearing organs is important for the prevention and treatment of ear diseases. In this review, we summarize the effects of viruses on signaling pathways and signaling molecules in the development of peripheral auditory organs.