Influenza viruses pose significant threats to public health and cause enormous economic loss every year. Previous work has revealed the viral factors that influence the virulence of influenza viruses. However, taking prior viral knowledge represented by heterogeneous categorical and discrete information into account is scarce in the existing work. How to make full use of the preceding domain knowledge into virulence study is challenging but beneficial. This paper proposes a general framework named ViPal for virulence prediction that incorporates discrete prior viral mutation and reassortment information based on all eight influenza segments. The posterior regularization technique is leveraged to transform prior viral knowledge to constraint features and integrated into the machine learning models. Experimental results on influenza genomic datasets validate that our proposed framework can improve virulence prediction performance over baselines. The comparison between ViPal and other existing methods shows the computational efficiency of our framework with superior performance. Moreover, the interpretable analysis through SHAP identifies the scores of constraint features contributing to the prediction. We hope this framework could provide assistance for the accurate detection of influenza virulence and facilitate flu surveillance.