UNC Researchers Identify a Viral Homolog to a Cellular Protein that Disrupts Inflammasome Function

Recent data published in the journal Science by Sean Gregory (graduate student in the Blossom Damania Lab), along with collaborators from the Jenny Ting Lab have identified a viral protein that masquerades as a normal cellular protein important in stopping viral infections...


Recent data published in the journal Science by Sean Gregory (graduate student in the Blossom Damania Lab), along with collaborators from the Jenny Ting Lab have identified a viral protein that masquerades as a normal cellular protein important in stopping viral infections. However, the Kaposi’s sarcoma-associated herpevirus (KSHV/HHV8) Orf63 protein inhibits, instead of activates, immune responses allowing viral reactivation and reproduction.


The formation of an inflammasome is an important event in initiating an appropriate immune response to infectious microbes. A cellular protein, NLRP1 (nucleotide binding and oligomerization, leucine-rich repeat, procaspase 1) is involved in the formation of the inflammasome during microbial infection. The inflammasome causes the activation of caspase-1 and processing of key interleukins. Gregory’s data demonstrates that the KSHV Orf63 protein is not only a homolog of NLRP1, but that it binds to, and inhibits, normal function of NLRP1. Gregory identified binding domains in KSHV Orf63 that are homologous to that of NLRP1, but lack key activation and recruitment domains. He also shows how KSHV Orf63 blocks the activation of caspase-1 and subsequent processing of IL-1β and IL-18, allowing viral escape from inflammasome responses. The function of KSHV Orf63 was uncharacterized prior to this data.