RNA processing and antiviral immunity

The RIG-I like receptors (RLRs) are intracellular enzyme sentries that detect viral infection and initiate a first line of antiviral defense. The cellular molecules that activate RLRs in vivo are not clear.

John Karijolich, Ph.D., and colleagues have made the surprising discovery that host-derived RNAs—not viral molecules—activate RLRs. The investigators studied the cellular response to infection with Kaposi’s sarcoma-associated herpesvirus (KSHV), an oncogenic virus and AIDS-associated pathogen that causes Kaposi’s sarcoma and primary effusion lymphoma (PEL).

In patient-derived PEL cells, the researchers demonstrated that RLRs restrict KSHV lytic reactivation—the viral replication and cell-destroying part of the viral life cycle. They found that RLRs sense host-derived noncoding RNAs, and that an infection-dependent reduction in another host protein results in the accumulation of noncoding RNAs that activate RLRs.

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