Historically, new pathogens of viral gastrointestinal infections in cattle were described based on electron microscopy results of faecal samples from newborn diarrheic calves. Subsequently, other methods, including molecular biology, began to be used for this purpose. Rotaviruses, coronaviruses, caliciviruses, toroviruses, astroviruses, kobuviruses, neboviruses and pestiviruses (causing bovine mucosal complex) were found in fecal samples from diarrheic calves using electron microscopy, molecular biology and fecal immunochemical test) [1][2][3][4][5][6][7][8][9][10][11][12][13]. A study of 269 fecal samples from sheep, goats, cattle, pigs and rabbits taken from livestock farms in Hungary revealed a new picornavirus, which was classified as Bopivirus genus [14].

Caliciviruses infecting a wide range of vertebrates, as well as humans, were separated from the Picornaviridae family in 1979 [12]. The Caliciviridae family unites a group of RNA viruses with similar morphology and different antigenic properties [15]. Caliciviruses are stable and highly resistant to physical and chemical exposures (factors) of the environment; remain infectious at pH 2.7 for 3 hours at room temperature. Viruses are resistant to ether, chloroform, guanidine, sodium deoxycholate, as well as to pH 4–5, and are active for 30 minutes when heated to 60 °C [3][15][16][17]. Calicivirus virions are small non-enveloped particles 27–40 nm in diameter with icosahedral symmetry (T = 3). A characteristic feature of calicivirus capsid architecture is 32 cup-shaped depressions at each of the icosahedral five-fold and three-fold axes (calyx is derived from the Latin which means cup). The molecular weight of the virion is 15 MDa, the sedimentation constant is 170–183 S, the buoyant density in CsCl gradient is 1.36–1.41 g/cm³. The capsid is comprised of 180 copies of the major capsid protein VP1 and 1–2 copies of the minor structural protein VP2, around the VPg-linked genome. VP1 dimers form 90 arch-shaped capsomers that form visible 40 Å deep and 90 Å wide depressions (cups). The genome of caliciviruses is positive-sense, single-stranded RNA with a molecular weight of 2.6–2.8 MDa and 7,500–7,700 bp in size. The infectivity of calicivirus RNA is caused by the VPg peptide covalently linked to genomic RNA [2][3][16][17][18][19][20]. The classification of caliciviruses was approved by the decision of the International Committee on Taxonomy of Viruses in 2002. This classification was based on the results of nucleotide sequence phylogenetic analysis [20][21][22]. Currently, the Caliciviridae family comprises pathogens belonging to eleven genera, among them noroviruses, neboviruses, sapoviruses, vesiviruses, lagoviruses, etc.1

In 1972, a new virus was discovered by immune electron microscopy in an infectious stool filtrate derived from an outbreak of human gastroenteritis in Norwalk, Ohio. The virus was named Norwalk virus [16][17][23], and the disease was named a norovirus infection. The results of numerous studies conducted in many countries indicate that all identified noroviruses have closely related genome structures, but are genetically and antigenically highly diverse and infect a wide range of mammalian host species including humans. This virus was detected in biological samples from cattle [24][25][26], pigs [12][27][28], sheep [29], cats [30][31], dogs [32][33], and mice [34].

Based on the phylogenetic analysis of the genome nucleotide sequences, noroviruses were classified into 7 genogroups [16][18][35]. Subsequently, separate clusters (genotypes) and genetic variants were recognized in each genogroup [11][16][18][20][35][36][37][38][39][40][41][42][43]. Noroviruses are characterized by rapid genetic variability [18]. The results of the VP1 phylogenetic analysis suggest that new norovirus strains emerge every 2–3 years and there is a risk of highly virulent strain occurrence. About 5% of Norwalk virus population evolve into new genetic variants every year [16][44]. Recombinations of caliciviruses are frequently reported, being the reason of antigenically altered viral strain emergence [16][39][45][46]. The Norwalk virus genome is prone to mutations, resulting in antigenic shifts and recombinations, as well as the emergence and rapid spread of new epidemic and epizootic variants [17][18][24][41][45]. The mutation processes involve the genome regions responsible for the virus binding to host receptors on the intestinal mucosal epithelium [16][41].

Epidemiological features of norovirus infection include: prolonged shedding of the virus by the diseased animals and carriers, various transmission routes (fecal-oral, contact) and high contagiousness [16][18]. Norovirus-contaminated feed and water can serve as transmission factors. The virus reservoir and source are infected (diseased and convalescent) animals. Bovine norovirus or human norovirus are responsible for the infection in cattle [24][28]. One gram of feces from a diseased animal contains 10⁸ viral particles or norovirus RNA copies [2][8][16][17][18][38]. It has been proven that the ingestion of 10 norovirus virions is sufficient for the development of clinical manifestations [8][16][17][18]. The norovirus infection incubation period in newborn calves infected with the virus isolated from cattle is 14–48 hours, the duration of the disease is from 2 to 30 days. Following the recovery, the virus is still shed for 5–50 days in the amount of 10⁴ copies of viral RNA per 1 g of feces. Calves infected with human norovirus start demonstrating clinical signs 2–6 days post infection [47].

Virions replicate and assemble in the cytoplasm, and viral particles are released when the cell is destroyed. The replication cycles of the caliciviruses are similar as far as they have been explored: viruses interact with a multitude of cell surface attachment factors (glycans) and co-receptors (proteins) for adsorption and penetration, use cellular membranes for the formation of replication complexes [48].

Noroviruses propagate in the epithelium cells of small intestinal villi, as well as the immune system cells (macrophages, dendritic cells, T and B-lymphocytes) [18][38][49][50][51]. At the same time, a broadening and blunting of the intestinal villi, epithelial cell peeling, crypt epithelial hyperplasia, cytoplasmic vacuolization, infiltration of the affected cells into the lamina propria are observed. The lesions are more severe in the small intestine (duodenum, jejunum and ileum), where mucosal inflammation involving atrophy of intestinal villi and hypertrophy of intestinal glands are detected. Decreased cell enzymatic activity and development of secondary disaccharide deficiency are observed. In the setting of this infection gastric motility disorder frequently occurs. Increased intestinal epithelial apoptosis, epithelial barrier malfunction, and development of diarrhea due to loss of ions and water from subepithelial capillaries into the lumen are observed [16][18]. Moreover, villous necrosis and villous atrophy are reported [38][45][50][51]. Norovirus was detected in the epithelial cells of the duodenum, jejunum and ileum, Peyer’s patches and large intestinal mesenteric lymph nodes [38].

Macroscopic lesions and clinical signs caused by norovirus infection are similar to those caused by rotavirus and coronavirus infections, which complicates clinical and post-mortem diagnosis [1][3][4][8][19][52]. Noroviruses are detected in fecal samples from cattle of different ages. The greatest economic losses are caused by norovirus infection in calves, who manifest diarrhea, depression, fever, and digestive disorders. Diarrhea is observed on days 3–7 post infection and can persist for a month. Diarrhoea is more severe in 3-week old calves than in neonatal animals [24]. In addition to norovirus, rota-, corona-, neboviruses, bovine diarrhea virus [53], and other microorganisms [10][11] were frequently isolated from fecal samples collected from diarrheic calves. When investigating the reasons of gastrointestinal disorders in newborn calves in England, Belgium, Hungary, Germany, Italy, the Netherlands, France, Slovenia, Norway, Sweden, China, South Korea, India, Iran, Turkey, Egypt, Tunisia, the USA, Australia and New Zealand, noroviruses were detected in faecal samples. The results of numerous tests suggested that norovirus infection is a highly contagious zoonotic disease with the fecal-oral route of transmission [11][20][28][29][36][38][39][40][41][44][49][53][54][55][56].

The table provides data on the detection of different norovirus genogroups in different hosts. Each norovirus genogroup comprises several genetic clusters (genotypes) depending on the similarity of genetic characteristics [45][57].

The results of the VP1 phylogenetic analyses suggest a high frequency of norovirus recombination. Noroviruses of genogroup II (GII) isolated from fecal samples of diseased humans and pigs are characterized by a high level of variability [16][12][28][58]. The study of genogroup GII norovirus RNA isolated from pig faecal samples in Japan, the USA and several European countries, revealed that porcine/human recombinants can emerge in subclinically infected adult animals, and pigs may be reservoirs of new human noroviruses [42][52][59].

Noroviruses have been shown to undergo extensive genetic recombination. Co-infection of calves with bovine and human strains of norovirus can produce a recombinant virus with altered virulence properties [46][60]. Noroviruses of genogroup GIII (bovine) and genotype GII.4 (human) were simultaneously identified in fecal samples from diarrheic calves in Canada [12].

There is a high probability that recombinant norovirus strains can emerge which potentially can transmit to human population.

The results of the experimental infection of gnotobiotic calves and piglets with human norovirus confirmed virus replication and seroconversion in infected animals [45][47]. Spontaneous infections of piglets with norovirus have been reported. In this case, diarrhea occurred 2–6 days after the experimental infection. The data from these studies led to the assumption that cattle and pigs may serve as a reservoir of human norovirus, due to viral mutations in the animal organism and emergence of strains with new properties. Long-term contacts between humans and viruses, which previously infected only animals, can lead to mutations and replication in the intestinal epithelium of the human [9][11][12][38][42][46][47][52][58][59][61]. It is believed that humans can be infected with bovine and porcine noroviruses through contaminated animal meat and milk [46]. The detection of human noroviruses in animals, as well as the simultaneous presence of human and animal noroviruses in bivalves, suggests a risk of the human norovirus transmission [62].

The results of serological tests showed antibodies to human norovirus in porcine sera in 36–71% of cases [27]. In the Netherlands, antibodies (IgG) to bovine norovirus were detected in 28 and 20% of serum samples, collected from 210 veterinarians and 630 animal owners, respectively [49]. In Sweden, 26.7% of blood donors were antibody-positive for bovine norovirus (GIII.2) [61]. It has been established that human norovirus has a clear tropism to the canine intestinal epithelial cells [18].

These data are based on the assumption that zoonotic transmission is typical for norovirus [20][45][46][59][61][63].