DR5 is a restriction factor for human herpesviruses.

Restriction factors are dominant proteins that target different essential steps of the viral life cycle; thus, these proteins provide an early line of defense against viruses. Here, we found that the internalization of DR5, an important receptor of the extrinsic apoptotic pathway, initiates apoptosis to inhibit Kaposi sarcoma-associated herpesvirus (KSHV) lytic replication. An evolutionary analysis of the DR5 sequence demonstrated that three amino acids underwent positive selection in primates.

The Interplay between KSHV Infection and DNA-Sensing Pathways.

During viral infection, the innate immune system utilizes a variety of specific intracellular sensors to detect virus-derived nucleic acids and activate a series of cellular signaling cascades that produce type I IFNs and proinflammatory cytokines and chemokines. Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic double-stranded DNA virus that has been associated with a variety of human malignancies, including Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. Infection with KSHV activates various DNA sensors, including cGAS, STING, IFI16, and DExD/H-box helicases.

KSHV RTA antagonizes SMC5/6 complex-induced viral chromatin compaction by hijacking the ubiquitin-proteasome system.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus with the capacity to establish life-long latent infection. During latent infection, the viral genome persists as a circular episome that associates with cellular histones and exists as a nonintegrated minichromosome in the nucleus of infected cells. Chromatin structure and epigenetic programming are required for the proper control of viral gene expression and stable maintenance of viral DNA.