Kaposi's sarcoma-associated herpesvirus internal ribosome entry site (IRES)

The Kaposi's sarcoma-associated herpesvirus internal ribosome entry site (KSHV IRES) is a ribonucleic acid (RNA) element found within the 5' untranslated region (5' UTR) of certain messenger RNAs (mRNAs) of the Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8). Unlike the canonical cap-dependent translation initiation mechanism utilized by most eukaryotic mRNAs, the KSHV IRES allows for translation initiation independently of the 5' cap structure.

The IRES element folds into a complex secondary and tertiary structure that directly recruits the ribosome to the mRNA, bypassing the need for scanning from the 5' end. This cap-independent translation is particularly important under conditions where cap-dependent translation is inhibited, such as during viral infection when the host cell's translation machinery is often targeted by viral strategies.

The KSHV IRES plays a critical role in the life cycle of the virus, facilitating the efficient expression of viral proteins, especially under cellular stress conditions. By enabling the translation of essential viral proteins even when general cellular translation is suppressed, the KSHV IRES contributes to viral replication, persistence, and ultimately, the development of Kaposi's sarcoma and other KSHV-associated malignancies. Different KSHV genes utilize IRES elements with varying efficiencies and dependencies on cellular trans-acting factors. Research on the KSHV IRES is focused on understanding its structure, function, and interactions with cellular proteins, with the goal of developing novel antiviral therapies that target IRES-mediated translation.