Introduction: History and Future of Ranaviruses

Abstract

Dr. Allan Granoff (1923–2012), who isolated the first ranavirus (Granoff et al. 1966), had, scattered throughout his office at St. Jude Children’s Research Hospital, a variety of frog-related items including the poem cited above. Although one of Allan’s isolates, Frog virus 3 (FV3), subsequently became the best-characterized member of both the genus (Ranavirus) and the family (Iridoviridae); the impact of that discovery was not fully appreciated at the time. FV3 was neither the first iridoviridae to be recognized as a pathogen of lower vertebrates or the first isolated. Those honors belonged to lymphocystis disease virus (LCDV) and Invertebrate iridovirus 1 (IIV1), respectively (Wissenberg 1965; Xeros 1954). LCDV is responsible for a generally non-life threatening, but disfiguring, disease in fish characterized by the appearance of wart-like growths on the skin and (rarely) internal organs, whereas IIV1 is the causative agent of latent and patent infections in crane fly larvae. Despite its lack of primacy, FV3 was studied because, in keeping with the mission of St. Jude Hospital, it was initially thought to be linked to adenocarcinoma in frogs and thus could be a useful model of human malignancies. Furthermore, unlike LCDV and IIV1, it could be readily grown in cultured cells and was thus amenable to detailed molecular characterization. Although its role in tumor development was soon proven incorrect, FV3 served as a gateway into understanding the replication strategy of a heretofore poorly studied virus family. Moreover, over the next 20 years, its study led to important insights not only into iridoviridae replication, but also eukaryotic biology, virus evolution, and host–virus interactions.