Toll-like receptor signaling controls reactivation of KSHV from latency
Year: 2009
Type: article
Abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease. Like other herpesviruses, KSHV establishes life-long latency in the human host with intermittent periods of reactivation. Physiological triggers of herpesviral reactivation are poorly defined. Toll-like receptors (TLRs) recognize pathogens and are vital for the host innate immune response. We screened multiple TLR agonists for their ability to initiate KSHV replication in latently infected PEL. Agonists specific for TLR7/8 reactivated latent KSHV and induced viral lytic gene transcription and replication. Furthermore, vesicular stomatitis virus (VSV), a bonafide physiological activator of TLR7/8, also reactivated KSHV from latency. This demonstrates that secondary pathogen infection of latently infected cells can reactivate KSHV. Human herpesviruses establish life-long latency in the host, and it is plausible that a latently infected cell will encounter multiple pathogens during its lifetime and that these encounters lead to episodic reactivation. Our findings have broad implications for physiological triggers of latent viral infections, such as herpesviral reactivation and persistence in the host.
Authors: Sean M. Gregory, John A. West, Patrick J. Dillon, Chelsey Hilscher, Dirk P. Dittmer, Blossom Damania
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1111229574, G1393734537, G1646449232, G1815638046, G2579308029, Innate Immunity and KSHV, KSHV Modulation of the Host Innate Immune System, Role of KSHV Viral Proteins in Signaling and Pathogenesis, G9000157954, G9000158818, G9000191358, G9000253134, Molecular Biology of Viral Diseases Predoctoral Training Grant, ART Modulation of Viral Pathogenesis
OpenAlex ID: W2010800481