Pathogenesis of GIII.2 bovine norovirus, CV186-OH/00/US strain in gnotobiotic calves

Abstract

The pathogenesis of GIII.2 bovine norovirus (BoNoV) is not well understood. Our study demonstrated persisting diarrhea and prolonged fecal shedding, but with a lack of significant intestinal lesions in gnotobiotic (Gn) calves infected with GIII.2 BoNoV, CV186-OH/00/US strain. Nine 4 to 7-day-old Angus/Jersey crossbred Gn calves were orally inoculated with 10.0-11.9 log10 genomic equivalents (GE)/calf of CV186-OH (n=7) or mock (n=2). Calves were euthanized at post-inoculation day (PID) 1 (n=1) when moderate to severe lethargy was observed and at PIDs 2-6 (n=4) after lethargy had subsided. Two calves were kept longer term (until PID 30) for monitoring fecal shedding patterns by TaqMan real-time RT-PCR (qRT-PCR). Most infected calves exhibited two clinical signs: i) acute but persisting diarrhea and ii) acute moderate to severe lethargy. The two infected calves, followed longer-term, had prolonged fecal viral RNA shedding [peak average titer of 11.8 (± 0.2) log10 GE/ml] at least until PID 20. By qRT-PCR, 5 infected calves had low viral RNA titers in serum, ranging from 4.0 to 5.8 log10 GE/ml, at PIDs 1-5, but not (<2.7 log10 GE/ml) at PIDs 6-30. The latter observation coincided with the presence of serum IgG antibody to BoNoV at PIDs 8-30. Collectively, the GIII.2 BoNoV strain CV186-OH induced only mild enteropathogenicity, evident by the lack of significant intestinal lesions, but it led to persisting mild diarrhea and prolonged fecal virus shedding in Gn calves. The prolonged fecal shedding of GIII.2 BoNoV might partially explain how this virus is maintained as endemic infections in cattle.

Enteric viral infections in lambs or kids

“…Caliciviruses belonging to at least three distinct genera of the family (Nebovirus, Norovirus, Vesivirus) have been identified in cattle (Smith et al, 2002;Oliver et al, 2003). Noroviruses and neboviruses have been associated with mild to moderate enteric signs and the infection and disease has been reproduced in gnotobiotic calves infected experimentally (Smiley et al, 2002;Jung et al, 2014). Also, gnotobiotic calves may be infected successfully with a human norovirus strain, although with limited replication and mild clinical signs (Souza et al, 2008).…”

Phylogeny of bovine norovirus in Egypt based on VP2 gene

“…BNoV was found in the feces of both diarrheic and healthy animals [2][3][4]. On experimental infection, gnotobiotic calves infected with BNoV showed various degrees of diarrhea and anorexia as a result of gastroenteritis [5,6].…”

Molecular detection of bovine Noroviruses in Argentinean dairy calves: Circulation of a tentative new genotype

“…Molecular detection of bovine Norovirus sequences has been frequently associated with calf diarrhea (Scipioni et al, 2008b). Their pathogenicity is believed to be low or moderate (Jung et al, 2014), although studies analyzing their economic impact (weight loss, health status, veterinary treatment cost) as co-infecting agent in combination with other enteric pathogens have not yet been conducted. Molecular characterizations of bovine Noroviruses circulating in cattle from different regions of the world have been performed but still there is scarce data regarding South American countries, where large cattle populations are living, such as Argentina or Brazil.…”