Conflicting Evidence between Clinical Perception and Molecular Epidemiology: The Case of Fowl Adenovirus D

Simple Summary The present study demonstrates the role of intensive poultry production in the rise of fowl adenovirus (FAdV), similar to what occurred for several multifactorial viral diseases of livestock. Although effective in limiting viral circulation, the applied control strategies, likely shaped its evolution. In fact, after the development and application of FAdV vaccines, an increase in evolutionary rate was observed and several sites and regions of the Hexon protein were proven under a significant pervasive or episodic diversifying selection, especially those exposed on the viral surface and target of the host response. The notion that FAdV has increased in relevance in the last years could thus be a misleading perception related to an increased diagnostic capability and awareness of the topic. Alternatively, a limited number of flocks could be more severely affected because of the waning population immunity. Further efforts should be devoted to the acquisition of more molecular data on other geographic regions and FAdV species, also to assess the representativeness of the present results on a broader scale.Abstract Fowl adenoviruses (FAdVs, species FAdV-A/-E) are responsible for several clinical syndromes reported with increasing frequency in poultry farms in the last decades. In the present study, a phylodynamic analysis was performed on a group of FAdV-D Hexon sequences with adequate available metadata. The obtained results demonstrated the long-term circulation of this species, at least several decades before the first identification of the disease. After a period of progressive increase, the viral population showed a high-level circulation from approximately the 1960s to the beginning of the new millennium, mirroring the expansion of intensive poultry production and animal trade. At the same time, strain migration occurred mainly from Europe to other continents, although other among-continent connections were estimated. Thereafter, the viral population declined progressively, likely due to the improved control measures, potentially including the development and application of FAdV vaccines. An increase in the viral evolutionary rate featured this phase. A role of vaccine-induced immunity in shaping viral evolution could thus be hypothesized. Accordingly, several sites of the Hexon, especially those targeted by the host response were proven under a significant pervasive or episodic diversifying selection. The present study results demonstrate the role of intensive poultry production and market globalization in the rise of FAdV. The applied control strategies, on the other hand, were effective in limiting viral circulation and shaping its evolution.