Virus Expression Database
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.
| 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 |