Science. 2011 Jan 21;331(6015):330-4.

Discovery of a viral NLR homolog that inhibits the inflammasome.External

Gregory, S. M., Davis, B. K., West, J. A., Taxman, D. J., Matsuzawa, S., Reed, J. C., Ting, J. P., Damania, B.,
--- - Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
The NLR (nucleotide binding and oligomerization, leucine-rich repeat) family of proteins senses microbial infections and activates the inflammasome, a multiprotein complex that promotes microbial clearance. Kaposi's sarcoma-associated herpesvirus (KSHV) is linked to several human malignancies. We found that KSHV Orf63 is a viral homolog of human NLRP1. Orf63 blocked NLRP1-dependent innate immune responses, including caspase-1 activation and processing of interleukins IL-1beta and IL-18. KSHV Orf63 interacted with NLRP1, NLRP3, and NOD2. Inhibition of Orf63 expression resulted in increased expression of IL-1beta during the KSHV life cycle. Furthermore, inhibition of NLRP1 was necessary for efficient reactivation and generation of progeny virus. The viral homolog subverts the function of cellular NLRs, which suggests that modulation of NLR-mediated innate immunity is important for the lifelong persistence of herpesviruses.
PMID: 21252346External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
CARD Caspase1 Link NLRP1 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 21252346
CARD NLRP1 Link NLRP1 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 21252346
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
CARD Caspase1 Link NLRP1 Caspase cleaved assay Caspase1 activation (Inflammasome) 21252346
(Link: click this icon to show interactions only between the two corresponding DDs)