The presence of propolis in the nest cavity of Apis mellifera L. provides numerous benefits to individual bee and overall colony immunity. Few studies have examined the effects of propolis on honey bee viruses, which are a contributing factor to increased colony mortality in many parts of the world. Propolis has activity against some viruses of human and veterinary significance; therefore, we wanted to test whether it could inhibit persistent infection of Deformed wing virus-A (DWV-A) and introduced infection of Acute bee paralysis virus (ABPV), two common honey bee pathogens, using the honey bee cell line, AmE-711. We also tested whether propolis acts directly on cellular immunity by quantifying levels of honey bee immune pathway genes. Levels of persistent DWV-A and introduced ABPV were quantified at 0, 3, 6, 12, and 24 hours after exposure to propolis extracts from two geographic sources. Propolis had an initial inhibitory effect on levels of ABPV, while levels of persistent DWV-A were unchanged. Exposure of honey bee cells to propolis resulted in variable immune responses. The AmE-711 cell culture system provides a good model to study the antiviral potential and immune modulating effects of propolis against honey bee disease at the cellular level.