Author Summary The mysterious outbreak of honey bee Colony Collapse Disorder (CCD) in the US in 2006–2007 has attracted massive media attention and created great concerns over the effects of various risk factors on bee health. Understanding the factors that are linked to the honey bee colony declines may provide insights for managing similar incidents in the future. We conducted this study to elucidate traits of a key honey bee virus, Israeli acute paralysis virus. We then developed an innovative strategy to control virus levels. The knowledge and insights gained from this study will have positive implications for bee disease management, helping to mitigate worldwide colony losses.