Ranaviruses: Not Just for Frogs

Ranaviruses (family Iridoviridae) were discovered serendipitously during an attempt to generate frog kidney cell cultures for the propagation of Lucke herpesvirus, an oncogenic herpesvirus [1]. Unexpectedly, some cultures displayed spontaneous cytopathic effect suggestive of a viral infection. Frog virus (FV)-1 and -2 were recovered from normal kidneys, whereas FV3, isolated from a frog with renal carcinoma, became the focus of further study. A number of “intriguing” features, i.e., a highly methylated genome, ability to rapidly turn-off host macromolecular synthesis, a circularly permuted/terminally redundant genome, the use of both host- and virus-encoded RNA polymerases, and absence of polyadenylated mRNA [2], fueled early FV3 study and provided insight into a poorly characterized family of nuclear, cytoplasmic, large DNA-containing viruses. However, because ranaviruses were not pathogenic for humans or commercially important animals, were not, as originally thought, oncogenic, and did not appear to have adverse long-term impacts on wildlife, FV3 research remained a viral backwater. Recent years have seen renewed interest in ranaviruses and other iridoviruses because they have been increasingly linked to die-offs, often marked, among cultured and wild fish, amphibians, and reptiles. Here, we review ranavirus replication and gene function, then focus on their impact on cold-blooded vertebrates.