Characterization of an Enteropathogenic Bovine Calicivirus Representing a Potentially New Calicivirus Genus

Abstract

Bovine enteric caliciviruses (BEC) are associated with diarrhea in young calves. The BEC strains detected in Europe form a third genogroup within the genus "Norwalk-like viruses" (NLV) of the family Caliciviridae. In this report, we present sequence, clinical, and histological data characterizing a novel enteropathogenic BEC strain, NB, detected in fecal specimens from calves in the United States. The complete RNA genome of the NB virus is 7,453 bases long and is organized into two open reading frames (ORFs). ORF-1 is 2,210 amino acids long and encodes a large nonstructural polyprotein contiguous with the major capsid protein (VP1), similar to the lagoviruses and "Sapporo-like viruses" (SLV). The conserved calicivirus motifs were identified in the nonstructural proteins. ORF-2 is located at the 3 end of the genome and encodes a small basic protein (VP2) of 225 amino acids. The 5 and 3 untranslated regions are 74 and 67 bases long, respectively. Among caliciviruses, NB virus shows amino acid identities of 14.1 to 22.6% over the entire ORF-1 nonstructuralprotein sequence with NLV, SLV, vesivirus, and lagovirus strains, while the overall sequence identity of the complete NB VP-1 with other caliciviruses is low, varying between 14.6 and 26.7%. Phylogenetic analysis of the complete VP1 protein, including strains from all four calicivirus genera, showed the closest grouping of NB virus to be with viruses in the genus Lagovirus, which cause liver infections and systemic hemorrhage in rabbits. In gnotobiotic calves, however, NB virus elicited only diarrhea and intestinal lesions that were most severe in the upper small intestine (duodenum and jejunum), similar to the NLV BEC strains. The tissues of major organs, including the lung, liver, kidney, and spleen, had no visible microscopic lesions.

Pathogenesis and Immune Responses in Gnotobiotic Calves after Infection with the Genogroup II.4-HS66 Strain of Human Norovirus

“…Also the elevated early proinflammatory TNF-␣ response likely prompted the subsequent high anti-inflammatory IL-10 serum responses. Our results may reflect the wider prevalence of NoVs (GIII) observed in association with diarrhea in young calves, reflecting their more pronounced susceptibility to NoV infection (45). However, both species of Gn animals (calves and pigs) appear to be suitable models for the study of HuNoV pathogenesis and host immune responses.…”

“…In comparison, experimental infection of Gn calves with a GIII NoV strain (Newbury agent 2) showed more severe lesions also in the jejunum (19). The Gn calves experimentally infected with an unrelated bovine enteric calicivirus (unassigned genogroup), strain NB, also had intestinal lesions that were more severe in the duodenum and jejunum and milder lesions in the ileum (45). We further detected HS66 capsid antigens in enterocytes of the jejunum and in smaller numbers in the ileum, with positive signals also being detected in macrophage-like Experimental NV infection of nonhuman primates showed that common marmosets and cotton top tamarins shed virus for only 2 days, and only one of four NV-inoculated rhesus macaques, which shed NV for a long period in the feces, developed serum NV-specific IgM and IgG Ab responses.…”

Molecular characterization of a novel astrovirus associated with disease in mink

“…As for other emerging viruses (Bowden et al, 2001;Haqshenas et al, 2001;Smiley et al, 2002;Todd et al, 2001), a range of amplification strategies designed for the determination of unknown sequences had to be applied to obtain the complete genome. It was important to perform this work using a single sample, despite limits of material, in order to avoid differences due to the possible sequence diversity among astrovirus strains present in the different samples.…”

“…This demonstrated the suitability of the chosen amplification protocol. Interestingly, we could only identify the second sequence as being derived from an astrovirus when we performed BLAST searches with the deduced amino acid sequence, indicating that sequence identities between astroviruses of different species are more prominent on the protein level than on the genomic level.As for other emerging viruses (Bowden et al, 2001; Haqshenas et al, 2001;Smiley et al, 2002;Todd et al, 2001), a range of amplification strategies designed for the determination of unknown sequences had to be applied to obtain the complete genome. It was important to perform this work using a single sample, despite limits of material, in order to avoid differences due to the possible sequence diversity among astrovirus strains present in the different samples.…”

Inter- and Intragenus Structural Variations in Caliciviruses and Their Functional Implications

“…The zoonotic potential of feline calicivirus has been suggested by the observation of a human antibody against it (53). More recently, the potential existence of animal reservoirs and the possibility of interspecies transmission have been suggested by the phylogenetic relatedness and classification of bovine and porcine viruses, isolated from the enteric tracts or fecal specimens of infected animals, within the genera Norovirus and Sapovirus, respectively (6,9,20,35,49,57,60).…”