Introduction: human enteric caliciviruses-an emerging pathogen whose time has come.

In 1972, the “Norwalk agent” was discovered in fecal specimens collected during the investigation of an outbreak of gastroenteritis at an elementary school in Norwalk, Ohio [1, 2]. While this was heralded as the discovery of the first virus specifically associated with gastroenteritis, research progressed slowly and the role of the Norwalk agent as an important pathogen remained in question because of the difficulty in detecting the virus. The virus was rarely seen by electron microscopy (EM), it could not be amplified in cell culture or in animal models, and many morphologically similar agents, referred to as either “small round structured viruses” (SRSVs) or “classic human caliciviruses,” were antigenically distinct and clearly different from the prototype Norwalk strain [3]. These viruses had been designated loosely by the location where each strain was detected (e.g., Hawaii, Snow Mountain, Sapporo, Taunton). Some immune diagnostics were developed on the basis of virus and antibody prepared from specimens collected from human volunteers, but these tests were of limited value outside of the research community. In the early 1990s, the cloning and sequencing of the Norwalk and Southampton viruses revolutionized the study of the human caliciviruses [4, 5]. Unlocking the genomic organization of this ill-defined group of viruses led immediately to the development of sensitive molecular diagnostics (e.g., reverse transcription–polymerase chain reaction, probes) that resulted in studies to better understand the epidemiology of these viruses [6, 7]. On the basis of their sequences, these viruses have now been placed into 2 provisionally named genera of the family Caliciviridae: “Norwalk-like viruses” (NLVs) and “Sapporolike viruses” (SLVs) [8]. In this classification, the viruses previously referred to as SRSVs are largely assigned to NLVs, but classic human caliciviruses fall into both the NLVs and the SLVs [9, 10]. With the new diagnostics, NLVs that had rarely been seen by EM of fecal samples from patients with acute gastroenteritis now emerged as the most common pathogens identified in outbreaks of gastroenteritis in those countries where a diagnosis was spe-