Computational aspects of transfusion-transmitted viruses

Abstract

Transfusion medicine has undergone many challenges in the past few decades, largely because of the threat of blood-borne diseases. In this study, Ross River virus (RRV), hepatitis B virus (HBV) and occult hepatitis B virus infection (OBI) were characterized using bioinformatics. Ross River virus is mainly transmitted by mosquitoes with around 5,000 cases in Australia annually. Ross River viraemia duration for asymptomatic infections was investigated by establishing an adult outbred Swiss mouse model. The results showed that Ross River viraemia duration could last up to nine days for asymptomatic infections, which provides a critical parameter to estimate RRV risk to blood safety. Based on published risk estimation models for West Nile virus (WNV) (which simulates some parameters pertaining to risks to blood safety) and dengue virus (DENV) (which uses a mathematical equation with fixed parameter values), a combined model was established to estimate RRV risk to blood safety. This combined model applied simulations in the WNV model to account for the uncertainties in the DENV model. The combined model is robust and calculated a RRV mean risk to blood safety of 0.98 (0.79-1.25) per 10,000 donations, similar to that of DENV. This result showed that some prevention methods, such as deferral of blood donors, should be implemented to further ensure blood safety. Hepatitis B virus is a well-established transfusion-transmitted virus. Hepatitis B surface antigen (HBsAg) was the first direct marker to be developed for blood screening for transfusion safety. Cost and other limitations associated with HBsAg diagnostic reagents could be obviated by the more effective use of routine pathology blood test data. Decision trees and logistic regression models were developed to predict HBsAg positive or negative. Alanine aminotransferase (ALT), albumin and alkaline phosphatase (ALKP) were identified as the critical parameters for HBsAg prediction. OBI is characterized by the presence of hepatitis B virus (HBV) DNA and the absence of detectable hepatitis B surface antigen. This project aimed to identify computationally the molecular evolutionary mechanism of OBI. This work showed that the amino acid variations in the surface antigen (S) region appear to play an important role in the molecular evolution of OBI. Amino acid variation in the S region also explains the limitations of hepatitis B surface antigen. immunoassays for detecting OBI strains. This will provide clues for diagnostic reagent design and HBV vaccine so that blood safety could be further ensured. Together these studies, using novel bioinformatic approaches, provide valuable information pertaining to threats associated with blood-borne diseases, contributing new knowledge to the fields of blood safety and transfusion medicine.

Date of Award	2014
Original language	English
Supervisor	Michelle Gahan (Supervisor), Alice Richardson (Supervisor), Brett Lidbury (Supervisor), Suresh Mahalingam (Supervisor) & Luby Simson (Supervisor)