The role of angiogenin in tRNA cleavage during Kaposi sarcoma-associated herpesvirus reactivation.

Kaposi sarcoma-associated herpesvirus (KSHV) is a human herpesvirus that is associated with several cancers, including Kaposi sarcoma and primary effusion lymphoma. KSHV changes how gene expression occurs in cells to support its replication. This thesis explores how infection-induced cleavage of transfer RNAs (tRNAs) might alter gene expression and protein expression. The cleaved RNA products, called tRFs, are found in cancers and in response to infection, alter gene and protein expression, and can be protective or harmful to cells. An increased number of tRFs were found during KSHV reactivation, or the switch from passive latent to active lytic infection. Angiogenin is the protein known to generate tRFs. Although angiogenin is known to support the passive state of infection (latency), we explored whether angiogenin or the tRFs it generates are antiviral. We found no evidence that angiogenin cuts these tRNAs or is antiviral. However, we posit that tRFs could still have an antiviral role in KSHV infection through a different mechanism that has yet to be explored. In summary, tRFs should be examined further for their antiviral effects, and novel biogenesis factors should be investigated.