Cytomegalovirus-induced pathology in human temporal bones with congenital and acquired infection

Tsuprun, Vladimir; Keskin, Nevra; Schleiss, Mark R.; Schachern, Pat; Cüreoğlu, Sebahattin

doi:10.1016/j.amjoto.2019.08.001

Cited by 11 publications

(14 citation statements)

References 43 publications

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“…Finally, although these specimens were likely derived from fetuses infected early in gestation, it is important to note that the precise timing of infection of structures in auditory pathways cannot be established with certainty, but only estimated. Most recently, autopsy specimens from two infants with cCMV infection who died during the perinatal period revealed similar findings, except that in one infant, the loss of outer hair cells was reported and infected cells were observed within the cochlear duct, although there was no evidence of virus infection in the hair cells [ 81 ]. Histologic changes were noted in the vestibular system with a loss of vestibular hair cells and HCMV inclusions seen in cells adjacent to the dark cells [ 81 ].…”

Section: Hearing Loss and Vestibular Dysfunction Following Congenital Hcmv Infectionsmentioning

confidence: 86%

“…Most recently, autopsy specimens from two infants with cCMV infection who died during the perinatal period revealed similar findings, except that in one infant, the loss of outer hair cells was reported and infected cells were observed within the cochlear duct, although there was no evidence of virus infection in the hair cells [ 81 ]. Histologic changes were noted in the vestibular system with a loss of vestibular hair cells and HCMV inclusions seen in cells adjacent to the dark cells [ 81 ]. Together, these studies demonstrate that HCMV can infect a variety of cell types within the inner ear, with the notable exception of hair cells of the Organ of Corti.…”

Section: Hearing Loss and Vestibular Dysfunction Following Congenital Hcmv Infectionsmentioning

confidence: 86%

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Murine Models of Central Nervous System Disease following Congenital Human Cytomegalovirus Infections

Moulden¹,

Sung

Brizić

et al. 2021

Pathogens

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Human cytomegalovirus infection of the developing fetus is a leading cause of neurodevelopmental disorders in infants and children, leading to long-term neurological sequela in a significant number of infected children. Current understanding of the neuropathogenesis of this intrauterine infection is limited because of the complexity of this infection, which includes maternal immunological responses that are overlaid on virus replication in the CNS during neurodevelopment. Furthermore, available data from human cases are observational, and tissues from autopsy studies have been derived from only the most severe infections. Animal models of this human infection are also limited by the strict species specificity of cytomegaloviruses. However, informative models including non-human primates and small animal models have been developed. These include several different murine models of congenital HCMV infection for the study of CMV neuropathogenesis. Although individual murine models do not completely recapitulate all aspects of the human infection, each model has provided significant information that has extended current understanding of the neuropathogenesis of this human infection. This review will compare and contrast different murine models in the context of available information from human studies of CNS disease following congenital HCMV infections.

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Section: Hearing Loss and Vestibular Dysfunction Following Congenital Hcmv Infectionsmentioning

confidence: 86%

Section: Hearing Loss and Vestibular Dysfunction Following Congenital Hcmv Infectionsmentioning

confidence: 86%

Murine Models of Central Nervous System Disease following Congenital Human Cytomegalovirus Infections

Moulden¹,

Sung

Brizić

et al. 2021

Pathogens

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“…Our lab has also demonstrated that host-derived ROS played a role in CMV-mediated SNHL, and that treatment with anti-oxidants reduced ROS, thereby improving hearing outcomes [ 131 ]. Viral latency and evidence of inflammation has also been observed within the human cochlea following CMV infection [ 132 , 133 ]. Together, these data suggest that in the absence of active viral infection, sustained inflammation from early life onwards contributes to degradation of cochlear function and SNHL.…”

Section: The Cochlea As a Model Organ To Study The Effect Of Early Life Inflammation On The Developing Hematopoietic And Immune Systemsmentioning

confidence: 99%

Early Life Inflammation and the Developing Hematopoietic and Immune Systems: The Cochlea as a Sensitive Indicator of Disruption

Otsuka

Nielson

Firpo

et al. 2021

Cells

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Emerging evidence indicates that perinatal infection and inflammation can influence the developing immune system and may ultimately affect long-term health and disease outcomes in offspring by perturbing tissue and immune homeostasis. We posit that perinatal inflammation influences immune outcomes in offspring by perturbing (1) the development and function of fetal-derived immune cells that regulate tissue development and homeostasis, and (2) the establishment and function of developing hematopoietic stem cells (HSCs) that continually generate immune cells across the lifespan. To disentangle the complexities of these interlinked systems, we propose the cochlea as an ideal model tissue to investigate how perinatal infection affects immune, tissue, and stem cell development. The cochlea contains complex tissue architecture and a rich immune milieu that is established during early life. A wide range of congenital infections cause cochlea dysfunction and sensorineural hearing loss (SNHL), likely attributable to early life inflammation. Furthermore, we show that both immune cells and bone marrow hematopoietic progenitors can be simultaneously analyzed within neonatal cochlear samples. Future work investigating the pathogenesis of SNHL in the context of congenital infection will therefore provide critical information on how perinatal inflammation drives disease susceptibility in offspring.

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“…The CMV may therefore penetrate the inner ear by this route and infect the marginal epithelial cells [ 19 ]. Nevertheless, histopathological studies are limited in adults [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…Active infection and inflammation were also found in the saccule and utricle, predominantly in the non-sensory epithelial cells such as the transitory cells and dark cells. Active CMV replication was noted in the inner ear epithelial cells, mesenchymal tissue, and bone marrow cells, but not in the highly differentiated neurons or sensorineural cells, according to experimental data [ 33 ]. In any case, establishing whether a virus (or another infectious agent) is relevant in the pathophysiology of a neurotological condition involves a claim beyond the plausibility of virulence and a significant association [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

A Systematic Review on the Association of Acquired Human Cytomegalovirus Infection with Hearing Loss

Martínez-Gómez

Pérez-Carpena

Flook

et al. 2020

JCM

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Congenital cytomegalovirus (CMV) infection induces a clinical syndrome usually associated with hearing loss. However, the effect of acquired CVM infection in adults and children has not been clearly defined. The objective of this review is to critically appraise scientific evidence regarding the association of acquired CMV infection with postnatal hearing loss or tinnitus. A systematic review of records reporting sensorineural hearing loss (SNHL) or tinnitus and acquired CMV infection including articles published in English was performed. Search strategy was limited to human studies with acquired CMV infection. After screening and quality assessment, nine studies involving 1528 individuals fulfilled the inclusion criteria. A total of 14% of patients with SNHL showed evidence of previous exposure to CMV, while in individuals without SNHL (controls) the percentage rose up to 19.3%. SNHL was reported as unilateral or bilateral in 15.3%, and not specified in 84.7% of cases. The degree of SNHL ranged from mild to profound for both children and adults. None of the records reported tinnitus. The prevalence of children or adults with acquired SNHL with a confirmed acquired CMV infection by Polymerase Chain Reaction (PCR) or IgM anti-CMV antibodies is low. Phenotyping of patients with acquired CMV infection was limited to hearing loss by pure tone audiometry and no additional audiological testing was performed in most of the studies. Additional symptoms deserve more attention, including episodic vertigo or tinnitus, since some patients with the clinical spectrum of Meniere Disease could result from a CMV latent infection.

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Cytomegalovirus-induced pathology in human temporal bones with congenital and acquired infection

Cited by 11 publications

References 43 publications

Murine Models of Central Nervous System Disease following Congenital Human Cytomegalovirus Infections

Murine Models of Central Nervous System Disease following Congenital Human Cytomegalovirus Infections

Early Life Inflammation and the Developing Hematopoietic and Immune Systems: The Cochlea as a Sensitive Indicator of Disruption

A Systematic Review on the Association of Acquired Human Cytomegalovirus Infection with Hearing Loss

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