Discovery of a Viral NLR Homolog that Inhibits the Inflammasome
Year: 2011
Type: article
Abstract: 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-1β and IL-18. KSHV Orf63 interacted with NLRP1, NLRP3, and NOD2. Inhibition of Orf63 expression resulted in increased expression of IL-1β 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.
Source: Science
Authors: Sean M. Gregory, Beckley K. Davis, John A. West, Debra J. Taxman, Shu-ichi Matsuzawa, John C. Reed, Jenny P. Y. Ting, Blossom Damania
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Colitis, Colon Cancer and the NLR Family, NLR Family Proteins: Mechanisms and Regulation, G2526215178, Innate Immunity and KSHV, KSHV Modulation of the Host Innate Immune System, Nucleotide Binding in NOD2-Mediated Inflammation and Carcinogenesis, Role of KSHV Viral Proteins in Signaling and Pathogenesis, Immunobiology of Acute Environmental Asthma, G7451320255, Southeast Regional Centers of Excellence for Biodefense & Emerging Infectious Di, Virulence Mechanisms of Viral Bcl-2 Homologs, Training in Sexually Transmitted Infections and HIV, Molecular Biology of Viral Diseases Predoctoral Training Grant
OpenAlex ID: W2058213975