Characterisation of the molecular mechanisms of hantavirus polymerase function

The Orthohantaviridae – more commonly simply known as hantaviruses – are a family of segmented negative-sense RNA viruses that contain many highly pathogenic zoonotic viruses.

While hantaviruses naturally circulate in rodents, shrews and bats where they cause asymptomatic and life-long chronic infections, some viruses can cause highly pathogenic disease in humans.

Severe cases of hantavirus-associated disease is characterized by ‘cytokine-storm’-like inflammatory disease, vascular leakage and haemorrhaging, acute renal or respiratory failure and death.

Case-fatality rates can reach up to 40%, with no licenced antiviral treatments or vaccines available yet.The viral RNA-dependent RNA polymerase is a highly conserved enzyme that is responsible for the transcription and replication of the viral RNA genome.

Despite the fact that it is the focal point of all viral processes that occur inside the host cell after virus entry and needs to interact with a multitude of both viral and host factors in an tightly regulated manner, we have only a very limited understanding of the molecular mechanisms of polymerase activity.

This project aims to characterise the molecular mechanisms of hantavirus polymerase activity at the single nucleotide and amino acid level, as well as utilize these findings towards understanding the host species barrier that prevents efficient human-to-human transmission and replication of highly pathogenic airborne hantaviruses.