Two misleading words in reports of virus discovery: little things mean a lot

An elegant definition of ‘‘virus’’ was made by Andre Lwoff in 1957 [1]. That definition is somewhat outdated in light of modern studies of viruses, but it remains a fascinating and erudite read. His extensive definition of a virus could be paraphrased as an entity (a) having nucleic acid, (b) replicating as nucleic acid only, (c) not growing or dividing but replicating by a template mechanism, (d) that does not possess its own energy system (provided by the host cell which it parasitizes), and (e) that is infectious. Numerous other definitions of ‘‘virus’’ have been published, for example that of Raoult and Forterre [2], who proposed that a virus is ‘‘a capsid-encoding organism that is composed of proteins and nucleic acids, self-assembles in a nucleocapsid and uses a ribosome-encoding organism for the completion of its life cycle’’. As far as we are aware, no definition of ‘‘virus’’ is exclusively based on genomics. Indeed, the late Nobel Laureate Sir Peter Medawar once succinctly put it as ‘‘bad news wrapped in protein’’ [3]. Improper use of the word ‘‘virus’’ somehow slips under the radar of some editors these days. Journals have published papers describing the molecular detection of nucleic acids, after which the authors sequence them and construct elaborate phylogenetic trees to determine whether they are from recognized or previously unrecognized viruses, and then incorrectly use the word ‘‘virus’’ when they should use the phrase ‘‘nucleic acid sequence’’ ([4–7]; numerous other citations could be presented). On the contrary, and as an example of proper use of terms and ingenious technique, the paper by Kruger et al. [8] reports a biological property of an ostensible henipavirus from an African bat, a virus which has not been isolated. Genomic RNA of this virus had been detected in fecal samples of a bat, the open reading frame of the fusion and attachment proteins of the putative virus were inserted into expression plasmids, and expression was compared to that of a well-characterized henipavirus from Malaysia. These surface glycoproteins then were shown to induce syncytium formation in bat cell cultures. Similarly ingenious techniques have been used to partially characterize other viruses before they were isolated [9, 10]. Still, complete phenotypic characterization awaits the isolation of a virus which can then be phenotyped. A virus comprises, in part, one or more RNA, DNA, or RNA ? DNA nucleic acid sequences, but there is more to a virus than that. Just as a forensic DNA sample is from a person, the sample is not the person from whom it was obtained. Without an actual virus isolate (difficult or perhaps impossible to obtain at this time for certain viruses), there is no virus to fully characterize. One may argue that a virus cannot be identified without an isolate; but this is a clear disregard of modern standards and is in contrast to modern concepts. Virus taxonomy now is based principally on virus genomics, the study of virus genes and their functions. Without knowledge of those genetic functions, nucleotide sequences are merely descriptions of chemical characteristics and do not provide phenotypic information C. H. Calisher (&) Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1690, USA e-mail: calisher@cybersafe.net