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.
A Human Stem Cell-Derived Neurosensory–Epithelial Circuitry on a Chip to Model Herpes Simplex Virus Reactivation / Mazzara, Pietro Giuseppe; Criscuolo, Elena; Rasponi, Marco; Massimino, Luca; Muggeo, Sharon; Palma, Cecilia; Castelli, Matteo; Clementi, Massimo; Burioni, Roberto; Mancini, Nicasio; Broccoli, Vania; Clementi, Nicola. - In: BIOMEDICINES. - ISSN 2227-9059. - 10:9(2022), p. 2068. [10.3390/biomedicines10092068]