Journal
BIOMEDICINES
Volume 10, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/biomedicines10092068
Keywords
reactivation; latency; herpes simplex virus; organoids; microfluidics; keratinocytes
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Funding
- European Research Council [340527, 842423]
- European Research Council (ERC) [842423] Funding Source: European Research Council (ERC)
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This study has developed a stable and reliable in vitro system that models the connectivity between different human sensory neurons and peripheral tissues. By analyzing the infection process of herpes simplex virus 1 (HSV-1), it provides a better understanding of viral latency and reactivation at the cellular and molecular levels.
Both emerging viruses and well-known viral pathogens endowed with neurotropism can either directly impair neuronal functions or induce physio-pathological changes by diffusing from the periphery through neurosensory-epithelial connections. However, developing a reliable and reproducible in vitro system modeling the connectivity between the different human sensory neurons and peripheral tissues is still a challenge and precludes the deepest comprehension of viral latency and reactivation at the cellular and molecular levels. This study shows a stable topographic neurosensory-epithelial connection on a chip using human stem cell-derived dorsal root ganglia (DRG) organoids. Bulk and single-cell transcriptomics showed that different combinations of key receptors for herpes simplex virus 1 (HSV-1) are expressed by each sensory neuronal cell type. This neuronal-epithelial circuitry enabled a detailed analysis of HSV infectivity, faithfully modeling its dynamics and cell type specificity. The reconstitution of an organized connectivity between human sensory neurons and keratinocytes into microfluidic chips provides a powerful in vitro platform for modeling viral latency and reactivation of human viral pathogens.
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