Human cytomegalovirus protein pUL36: A dual cell death pathway inhibitor.

ABSTRACT: Human cytomegalovirus (HCMV) is an important human pathogen and a paradigm of intrinsic, innate, and adaptive viral immune evasion. Here, we employed multiplexed tandem mass tag-based proteomics to characterize host proteins targeted for degradation late during HCMV infection. This approach revealed that mixed lineage kinase domain-like protein (MLKL), a key terminal mediator of cellular necroptosis, was rapidly and persistently degraded by the minimally passaged HCMV strain Merlin but not the extensively passaged strain AD169. The strain Merlin viral inhibitor of apoptosis pUL36 was necessary and sufficient both to degrade MLKL and to inhibit necroptosis. Furthermore, mutation of pUL36 Cys¹³¹ abrogated MLKL degradation and restored necroptosis. As the same residue is also requi

SUBMITTER: Fletcher-Etherington A 

PROVIDER: S-EPMC7414183 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature