643476 (Evaluate) and ZonMW TOP task 91213058. Conflicts appealing The authors declare no conflict appealing.. Noroviruses are grouped into at least seven genogroups (GICGVII) that are additional divided into a lot more than 40 genotypes [1]. The trojan contains three open up reading structures (ORFs), ORF1 encoding the polyprotein which includes the viral polymerase, and ORF3 and ORF2 encoding the main- and minimal capsid proteins (VP1, VP2), [2] respectively. Recombination between ORF1 and ORF2 often occurs and for that reason a dual nomenclature explaining both polymerase and capsid genotype can be used [3,4,5]. Infections from genogroups GI, GII and GIV are recognized to infect human beings. Animal noroviruses including viruses found in pigs, dogs, and cats are closely related to human strains and cluster within Diflumidone GII (porcine norovirus) and GIV (feline and canine norovirus), respectively [1]. Noroviruses belonging to the other genogroups infect a broad range of hosts that includes livestock animals such as cows and sheep but also marine mammals and rodents. In the past years, an increasing number of metagenomic studies have led to the discovery of additional noroviruses in new animal hosts and it seems evident that we lack understanding of the full diversity of noroviruses and their host range [6,7]. Most human infections and outbreaks are caused by viruses belonging to GI and GII. The GII.4 genotype viruses have been particularly prevalent in the past two decades, and evolve through accumulation of mutations but also by recombination. Such recombinants and other new genotypes emerge regularly but the origin of these new viruses is not well comprehended LEPR [8]. This regular detection of novel strains and the reporting of human-like norovirus genotypes in stool Diflumidone samples of symptomatic and asymptomatic farm animals have sparked interest in the possible role of animals as potential zoonotic reservoir for these emerging strains [9,10,11,12]. Antibodies directed against bovine and canine norovirus have been detected in humans suggesting some level of exposure of humans to animal norovirus [13,14,15,16]. For other viruses of the family, interspecies transmission has been reported including some case reports of zoonotic events between marine mammals and humans (reviewed in [17]). This systematic review summarizes the literature around the known animal reservoir for norovirus, the virus diversity, prevalence, and geographic distribution, as well as pathological findings associated with norovirus infections in animals. We will further discuss the existing evidence and probability of interspecies transmission including susceptibility of animals used as models in norovirus research. There are several reviews that focus exclusively around the role of mice in norovirus research [18,19,20]; therefore, we will discuss murine norovirus only in context of surveillance of wild animals. Molluscs are an important vehicle of foodborne norovirus transmission, but do not support norovirus replication and have been reviewed elsewhere [21,22]. 2. Results 2.1. Search Output: The search yielded 6702 papers of which a total of 182 were included in the review. An additional nine papers were later included (see methods). 2.2. Noroviruses in Domesticated and Wild Animals Norovirus was first described from a gastroenteritis outbreak in 1968, which affected children in a school in Norwalk, Ohio, USA [23]. In 1972, the virus was visualized for the first time by immune electron microscopy revealing small round structured viruses (SRSV) of 27C35 nm in diameter, which was used as their first classification [24]. Viruses of comparable morphology were soon described from stool samples of domestic calves and pigs, and sequencing confirmed the presence of viruses belonging to the same family as human noroviruses. To date, porcine noroviruses are genetically most similar to human norovirus; porcine noroviruses have been classified among a diverse range of human norovirus genotypes in GII as GII.11 (prototype SW918), GII.18 and GII.19 Diflumidone [10,25] and have been found in stools and intestinal content of pigs all over Europe, North and South America, and Asia (Figure 1A,B, Table 1). Open in a separate window Physique 1 Studies describing the presence of animal norovirus across the world. (A) Countries in which animal norovirus have been detected are colored green. Each dot represents a study and location where animals have been found positive by either RT-PCR, real-time RT-PCR, or serology. The color indicates the host. (B) Number (n) of publications Diflumidone reporting positive versus unfavorable surveillance.