Virus Expression Database

GSE136586

Kallikrein-mediated cytokeratin 10 degradation is required for VZV propagation in skin

Submitted by Ryan O'Shaughnessy (Queen Mary University of London, United Kingdom) on Aug 28 2019

Platform: ngs – NextSeq 550 (Homo sapiens)

Pubmed: 31626786

Summary Varicella Zoster Virus (VZV) is a skin-tropic virus that infects epidermal keratinocytes and causes chickenpox. Although common, VZV infection can be life-threatening particularly in the immunocompromised. Therefore, understanding VZV-keratinocyte interactions is important to find new treatments beyond vaccination and anti-viral drugs. In VZV- infected skin, Kallikrein 6 (KLK6), and the ubiquitin-ligase MDM2 are up-regulated concomitant with Keratin 10 (K10) down-regulation. MDM2 binds to K10 targeting it for degradation via the ubiquitin-proteasome pathway. Preventing K10 degradation reduced VZV propagation in culture and prevented epidermal disruption in skin explants. K10 knockdown induced expression of the nuclear receptor subfamily 4, group A, member 1 (NR4A1) and enhanced viral propagation in culture. NR4A1 knockdown prevented viral propagation in culture, reduced LC3 levels and increased LAMP2 expression. We therefore describe a novel drug-able pathway whereby MDM2 ubiquitinates and degrades K10 increasing NR4A1 expression allowing VZV replication and propagation.

12 Samples

ID Title Cell Type Timepoint Reported Virus Virus Species Exclusion Reason
GSM4052311 Uninf 1 melanoma cell line  [MeWo ] none Uninfected
GSM4052312 Uninf 2 melanoma cell line  [MeWo ] none Uninfected
GSM4052313 Uninf 3 melanoma cell line  [MeWo ] none Uninfected
GSM4052314 VZV1 melanoma cell line  [MeWo ] unknown VZV pOka Human alphaherpesvirus 3
GSM4052315 VZV2 melanoma cell line  [MeWo ] unknown VZV pOka Human alphaherpesvirus 3
GSM4052316 VZV3 melanoma cell line  [MeWo ] unknown VZV pOka Human alphaherpesvirus 3
GSM4052317 VZV+Nutlin 1 melanoma cell line  [MeWo ] unknown VZV pOka Human alphaherpesvirus 3 Extra interventions
Nutlin-3 treated
GSM4052318 VZV+Nutlin 2 melanoma cell line  [MeWo ] unknown VZV pOka Human alphaherpesvirus 3 Extra interventions
Nutlin-3 treated
GSM4052319 VZV+Nutlin 3 melanoma cell line  [MeWo ] unknown VZV pOka Human alphaherpesvirus 3 Extra interventions
Nutlin-3 treated
GSM4052320 Uninf+Nutlin 1 melanoma cell line  [MeWo ] none Uninfected Extra interventions
Nutlin-3 treated
GSM4052321 Uninf+Nutlin 2 melanoma cell line  [MeWo ] none Uninfected Extra interventions
Nutlin-3 treated
GSM4052322 Uninf+Nutlin 3 melanoma cell line  [MeWo ] none Uninfected Extra interventions
Nutlin-3 treated