Embryonic and Neonatal Mouse Cochleae Are Susceptible to Zika Virus Infection.

Congenital Zika Syndrome (CZS) is caused by vertical transmission of Zika virus (ZIKV) to the gestating human fetus. A subset of CZS microcephalic infants present with reduced otoacoustic emissions; this test screens for hearing loss originating in the cochlea. This observation leads to the question of whether mammalian cochlear tissues are susceptible to infection by ZIKV during development. To address this question using a mouse model, the sensory cochlea was explanted at proliferative, newly post-mitotic or maturing stages. ZIKV was added for the first 24 h and organs cultured for up to 6 days to allow for cell differentiation. Results showed that ZIKV can robustly infect proliferating sensory progenitors, as well as post-mitotic hair cells and supporting cells. Virus neutralization using ZIKV-117 antibody blocked cochlear infection. AXL is a cell surface molecule known to enhance the attachment of flavivirus to host cells. While Axl mRNA is widely expressed in embryonic cochlear tissues susceptible to ZIKV infection, it is selectively downregulated in the post-mitotic sensory organ by E15.5, even though these cells remain infectible. These findings may offer insights into which target cells could potentially contribute to hearing loss resulting from fetal exposure to ZIKV in humans.

Hallazgos otoneurológicos en pacientes portadores de VIH y neurosífilis / Otoneurological findings in HIV and neurosyphilis coinfected patients

Introducción: El virus de la inmunodeficiencia humana (VIH) y el Treponema pallidum comparten mecanismos de transmisión y tienen la potencialidad de cambiar el curso de la otra enfermedad. Entre el 1% y 13% de los pacientes infectados con VIH presentan serología positiva para sífilis o desarrollan la enfermedad durante la evolución. Ambas pueden causar un variado número de alteraciones cocleovestibulares. Objetivo: Describir los hallazgos otoneurológicos en pacientes infectados con VIH y con presentación de neurosífilis durante la evolución de su enfermedad. Material y método: Estudio transversal observacional en 10 pacientes VIH positivos con episodios de neurosífilis de la Unidad de Infectología del Hospital Sótero del Río. Se realizó consulta otorrinolaringológica y examen funcional del octavo par con video-óculo-nistagmografía. Resultados: Sesenta por ciento de los pacientes infectados con VIH y neurosífilis presentó síntomas cocleovestibulares, de los cuales todos presentaron alteraciones audiométricas, 50%% de la muestra, además, presentó alteraciones vestibulares de características periféricas. El síntoma más frecuente fue la hipoacusia (50%%). La alteración audiométrica más frecuente fue la hipoacusia sensorioneural bilateral asimétrica. No se observó predominancia de algún tipo de alteración vestibular. Ningún paciente presentó alteraciones centrales. Conclusión: La evaluación otorrinolaringológica debiera considerarse como de rutina para disminuir la discapacidad generada por patología otoneurológica en estos pacientes.

Introduction: The human immunodeficiency virus (HIV) and Treponema pallidum share transmission mechanisms and have the potentiality of changing one another courses. Between 1 and 13%% of HIV infected patients present positive serology for syphilis or develop this disease during the evolution of the HIV. Both can cause a wide range of cochleovestibular manifestations. Aim: To describe otoneurological findings in HIV patients with episodes of neurosyphilis during the course of the disease. Material and method: Observational transversal study with 10 HIVpositive patients with episodes of neurosyphilis registered in the Infectology Unit of Sótero del Río Hospital. They went under otolaryngologic consult and functional testing of vestibulochoclear nerve with videonystagmography. Results: 60%% of evaluated patients had cochleovestibular symptoms, all of them with audiometric alterations. 50% of the sample also showed vestibular abnormalities (peripheral disorders). The commonest symptom was hearing loss (50%%). The most frequent audiometric alteration was asymmetric bilateral neurosensorial hearing loss. We did not observe any kind of vestibular variation predominance. No patient presented central vestibular disease. Conclusions: The otolaryngologic evaluation should be considered as a routine exam to diminish the disability generated in these patients because of the acquired otoneurological disease.

A glucocorticoid reduces adverse effects of adenovirus vectors in the cochlea.

Gene transfer using a recombinant adenovirus is a powerful tool for research and clinical applications, but its cytotoxicity and immune response limit its use, especially when repeated application of the vector is necessary. This study investigated the effects of dexamethasone (DEX)-induced immunosuppression on the outcome of adenovirus gene transfer in guinea pig inner ears. Animals received DEX for 29 days. Their inner ear was inoculated with 5 micro l of adenovirus vector twice, on days 5 and 26. Auditory brainstem response was measured on days 1, 8 and 29. The animals were sacrificed on day 29, and reporter gene expression was evaluated. In control animals that received no DEX, postinoculation threshold shifts and lesions in the organ of Corti were observed and reporter gene expression was absent. In contrast, DEX-treated ears were largely protected, and transduction of inner ear cells was readily apparent. These data demonstrate that immunosuppressive treatment can reduce the negative consequences of repeated adenovirus-mediated gene therapy.

Late sequelae of cochlear infection.

Inflammatory reactions within the inner ear are deleterious to cochlear function and can result in server hearing loss that does not recover. This study investigated a guinea pig model of long-term cytomegalovirus infection. At high doses active inflammation was still present after 35 days. At lower doses some ears showed partial resolution while others were still inflamed. Hearing was totally lost in all cases of persistent inflammation. There was some residual hearing in the cases that had resolved. Cochlear structures including the organ of Corti, stria vascularis, and spiral ganglion were partially degenerated. Fibrotic matrix within scala tympani was ossified in many cases. These changes are consistent with those described for human cochleas following putative viral infections.