Investigating the Role of Hypusine in Viral Translation and Infection

Polyamines are small, positively charged, molecules found in eukaryotic cells with roles in cellular function and viral infection. in previous work we have shown RNa viruses, including bunyaviruses, to be sensitive to polyamine depletion, but exact mechanisms are unknown. Bunyaviruses are emerging pathogens that cause encephalitis, hemorrhagic fevers, and meningitis. Rift Valley Fever Virus is a bunyavirus that infects both humans and livestock with severe mortality and morbidity. in previous work done with Rift Valley Fever Virus polyamine depleted results in noninfectious interfering particles without affecting the shape or size of the particles. Here, I investigate a specific metabolic pathway reliant on polyamines called hypusination. Hypusine is a unique amino acid found in eukaryotic cells with roles in protein production, protein trafficking, and inflammation. Using Rift Valley Fever Virus (vaccine strain MP-12) we found depletion of hypusinated-eIF5a lowered viral titer and protein production during infection. Anti-hypusination drugs do not alter the cellular polyamine profile and have no direct activity on the virus. in sum, depletion of hypusine lowers viral protein production without altering cellular polyamine levels to lower viral titers