Hearing Loss Caused by HCMV Infection through Regulating the Wnt and Notch Signaling Pathways

Huang, Shengnan; Zhou, Yuepeng; Jiang, Xuan; Yang, Bo; Cheng, Han; Luo, Min‐Hua

doi:10.3390/v13040623

Cited by 7 publications

(2 citation statements)

References 80 publications

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“…Congenital human cytomegalovirus (HCMV) infection is the leading cause of birth defects, affecting 0.5-3% of newborns worldwide [1,2]. Up to 20% of congenital-infected infants will show symptoms or develop long-term neurologic conditions, including microcephaly, cerebral palsy, hearing loss, etc [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Human cytomegalovirus pUL97 upregulates SOCS3 expression via transcription factor RFX7 in neural progenitor cells

et al. 2023

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Congenital human cytomegalovirus (HCMV) infection causes severe damage to the fetal brain, and the underlying mechanisms remain elusive. Cytokine signaling is delicately controlled in the fetal central nervous system to ensure proper development. Here we show that suppressor of cytokine signaling 3 (SOCS3), a negative feedback regulator of the IL-6 cytokine family signaling, was upregulated during HCMV infection in primary neural progenitor cells (NPCs) with a biphasic expression pattern. From viral protein screening, pUL97 emerged as the viral factor responsible for prolonged SOCS3 upregulation. Further, by proteomic analysis of the pUL97-interacting host proteins, regulatory factor X 7 (RFX7) was identified as the transcription factor responsible for the regulation. Depletion of either pUL97 or RFX7 prevented the HCMV-induced SOCS3 upregulation in NPCs. With a promoter-luciferase activity assay, we demonstrated that the pUL97 kinase activity and RFX7 were required for SOCS3 upregulation. Moreover, the RFX7 phosphorylation level was increased by either UL97-expressing or HCMV-infection in NPCs, suggesting that pUL97 induces RFX7 phosphorylation to drive SOCS3 transcription. We further revealed that elevated SOCS3 expression impaired NPC proliferation and migration in vitro and caused NPCs migration defects in vivo. Taken together, these findings uncover a novel regulatory mechanism of sustained SOCS3 expression in HCMV-infected NPCs, which perturbs IL-6 cytokine family signaling, leads to NPCs proliferation and migration defects, and consequently affects fetal brain development.

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Section: Introductionmentioning

confidence: 99%

Human cytomegalovirus pUL97 upregulates SOCS3 expression via transcription factor RFX7 in neural progenitor cells

et al. 2023

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“…Huang et al analyzed the factors that could be responsible for this complication, including the interaction of hCMV with the Wnt and Notch signaling pathways, involved in inner ear development. They highlighted the need to further investigate this issue to provide new directions for therapeutic development [ 45 ].…”

Section: Introductionmentioning

confidence: 99%

Development of a Vaccine against Human Cytomegalovirus: Advances, Barriers, and Implications for the Clinical Practice

et al. 2021

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Human cytomegalovirus (hCMV) is one of the most common causes of congenital infection in the post-rubella era, representing a major public health concern. Although most cases are asymptomatic in the neonatal period, congenital CMV (cCMV) disease can result in permanent impairment of cognitive development and represents the leading cause of non-genetic sensorineural hearing loss. Moreover, even if hCMV mostly causes asymptomatic or pauci-symptomatic infections in immunocompetent hosts, it may lead to severe and life-threatening disease in immunocompromised patients. Since immunity reduces the severity of disease, in the last years, the development of an effective and safe hCMV vaccine has been of great interest to pharmacologic researchers. Both hCMV live vaccines—e.g., live-attenuated, chimeric, viral-based—and non-living ones—subunit, RNA-based, virus-like particles, plasmid-based DNA—have been investigated. Encouraging data are emerging from clinical trials, but a hCMV vaccine has not been licensed yet. Major difficulties in the development of a satisfactory vaccine include hCMV’s capacity to evade the immune response, unclear immune correlates for protection, low number of available animal models, and insufficient general awareness. Moreover, there is a need to determine which may be the best target populations for vaccine administration. The aim of the present paper is to examine the status of hCMV vaccines undergoing clinical trials and understand barriers limiting their development.

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Genome-wide DNA methylation analysis of middle-aged and elderly monozygotic twins with age-related hearing loss in Qingdao, China

Guo

Wang

Song

et al. 2023

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Hearing Loss Caused by HCMV Infection through Regulating the Wnt and Notch Signaling Pathways

Cited by 7 publications

References 80 publications

Human cytomegalovirus pUL97 upregulates SOCS3 expression via transcription factor RFX7 in neural progenitor cells

Human cytomegalovirus pUL97 upregulates SOCS3 expression via transcription factor RFX7 in neural progenitor cells

Development of a Vaccine against Human Cytomegalovirus: Advances, Barriers, and Implications for the Clinical Practice

Genome-wide DNA methylation analysis of middle-aged and elderly monozygotic twins with age-related hearing loss in Qingdao, China

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