Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis.
Cell Rep
; 37(13): 110144, 2021 12 28.
Article
de En
| MEDLINE
| ID: mdl-34965440
ABSTRACT
Kaposi's sarcoma herpesvirus (KSHV) is an angiogenesis-inducing oncovirus whose ability to usurp the oxygen-sensing machinery is central to its oncogenicity. By upregulating the hypoxia-inducible factors (HIFs), KSHV reprograms infected cells to a hypoxia-like state, triggering angiogenesis. Here we identify a link between KSHV replicative biology and oncogenicity by showing that KSHV's ability to regulate HIF2α levels and localization to the endoplasmic reticulum (ER) in normoxia enables translation of viral lytic mRNAs through the HIF2α-regulated eIF4E2 translation-initiation complex. This mechanism of translation in infected cells is critical for lytic protein synthesis and contributes to KSHV-induced PDGFRA activation and VEGF secretion. Thus, KSHV regulation of the oxygen-sensing machinery allows virally infected cells to initiate translation via the mTOR-dependent eIF4E1 or the HIF2α-dependent, mTOR-independent, eIF4E2. This "translation initiation plasticity" (TRIP) is an oncoviral strategy used to optimize viral protein expression that links molecular strategies of viral replication to angiogenicity and oncogenesis.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Initiation de la traduction
/
Sarcome de Kaposi
/
Réplication virale
/
Herpèsvirus humain de type 8
/
Facteurs de transcription à motif basique hélice-boucle-hélice
/
Carcinogenèse
/
Hypoxie
Type d'étude:
Prognostic_studies
Limites:
Humans
Langue:
En
Journal:
Cell Rep
Année:
2021
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique