Background Tissue culture-adapted Tulane virus (TV), a GI.1 rhesus enteric calicivirus (ReCV), and a mixture of GII.2 and GII.4 human norovirus (NoV)-containing stool sample were used to intrastomacheally inoculate juvenile rhesus macaques (Macaca mulatta) in order to evaluate infection caused by these viruses. Methodology & Findings Two of the three TV-inoculated macaques developed diarrhea, fever, virus-shedding in stools, inflammation of duodenum and 16-fold increase of TV-neutralizing (VN) serum antibodies but no vomiting or viremia. No VN-antibody responses could be detected against a GI.2 ReCV strain FT285, suggesting that TV and FT285 represent different ReCV serotypes. Both NoV-inoculated macaques remained asymptomatic but with demonstrable virus shedding in one animal. Examination of duodenum biopsies of the TV-inoculated macaques showed lymphocytic infiltration of the lamina propria and villous blunting. TV antigen-positive (TV+) cells were detected in the lamina propria. In most of the TV+ cells TV co-localized perinuclearly with calnexin – an endoplasmic reticulum protein. A few CD20+TV+ double-positive B cells were also identified in duodenum. To corroborate the authenticity of CD20+TV+ B cells, in vitro cultures of peripheral blood mononuclear cells (PBMCs) from healthy macaques were inoculated with TV. Multicolor flow cytometry confirmed the presence of TV antigen-containing B cells of predominantly CD20+HLA-DR+ phenotype. A 2-log increase of viral RNA by 6 days post inoculation (p<0.05) suggested active TV replication in cultured lymphocytes. Conclusions/Significance Taken together, our results show that ReCVs represent an alternative cell culture and animal model to study enteric calicivirus replication, pathogenesis and immunity.
References
[1]
Farkas T, Sestak K, Wei C, Jiang X (2008) Characterization of a rhesus monkey calicivirus representing a new genus of Caliciviridae. J Virol 82: 5408–5416.
[2]
L'Homme Y, Sansregret R, Plante-Fortier E, Lamontagne AM, Ouardani M, et al. (2009) Genomic characterization of swine caliciviruses representing a new genus of Caliciviridae. Virus Genes 39: 66–75.
[3]
Wolf S, Reetz J, Otto P (2011) Genetic characterization of a novel calicivirus from a chicken. Arch Virol 156: 1143–1150.
[4]
Patel MM, Hall AJ, Vinjé J, Parashar UD (2009) Noroviruses: A comprehensive review. J Clin Virol 44: 1–8.
[5]
Scallan E, Hoekstra RM, Angulo FJ, Tauxe RV, Widdowson MA, et al. (2011) Foodborne illness acquired in the United States – major pathogens. Emerg Infect Dis 17: 7–15.
[6]
Atmar RL (2010) Noroviruses – State of the Art. Food Environ Virol 2: 117–126.
Wyatt RG, Greenberg HB, Dalgard DW, Allen WP, Sly DL, et al. (1978) Experimental infection of chimpanzees with the Norwalk agent of epidemic viral gastroenteritis. J Med Virol 2: 89–96.
[9]
Cheetham S, Souza M, Meulia T, Grimes S, Han MG, et al. (2006) Pathogenesis of a genogroup II human norovirus in gnotobiotic pigs. J Virol 80: 10372–10381.
[10]
Rockx BH, Bogers WM, Heeney JL, van Amerongen G, Koopmans MP (2005) Experimental norovirus infections in non-human primates. J Med Virol 75: 313–320.
[11]
Souza M, Azevedo MS, Jung K, Cheetham S, Saif LJ (2008) Pathogenesis and immune responses in gnotobiotic calves after infection with the genogroup II.4-HS66 strain of human norovirus. J Virol 82: 1777–1786.
[12]
Subekti DS, Tjaniadi P, Lesmana M, McArdle J, Iskandriati D, et al. (2002) Experimental infection of Macaca nemestrina with a Toronto Norwalk-like virus of epidemic viral gastroenteritis. J Med Virol 66: 400–406.
[13]
Wobus CE, Karst SM, Thackray LB, Chang KO, Sosnovtsev SV, et al. (2004) Replication of Norovirus in cell culture reveals a tropism for dendritic cells and macrophages. PLoS Biol 2: e432.
[14]
Cannon JL, Lindesmith LC, Donaldson EF, Saxe L, Baric RS, et al. (2009) Herd immunity to GII.4 noroviruses is supported by outbreak patient sera. J Virol 83: 5363–5374.
[15]
Lindesmith L, Moe C, Lependu J, Frelinger JA, Treanor J, et al. (2005) Cellular and humoral immunity following Snow Mountain virus challenge. J Virol 79: 2900–2909.
[16]
Hutson AM, Altmar RL, Graham DY, Estes MK (2002) Norwalk virus infection and disease is associated with ABO histo-blood group type. J Infect Dis 185: 1335–1337.
[17]
Lindesmith L, Moe C, Marionneau S, Ruvoen N, Jiang X, et al. (2003) Human susceptibility and resistance to Norwalk virus infection. Nat Med 9: 548–553.
[18]
Tan M, Jiang X (2010) Norovirus gastroenteritis, carbohydrate receptors, and animal models. PLoS Pathog 6: e1000983.
[19]
Farkas T, Cross RW, Hargitt E, Lerche NW, Morrow AL, et al. (2010) Genetic diversity and histo-blood group antigen interactions of rhesus enteric caliciviruses. J Virol 84: 8617–8625.
[20]
Barron EL, Sosnovtsev SV, Bok K, Prikhodko V, Sandoval-Jaime C, et al. (2011) Diversity of murine norovirus strains isolated from asymptomatic mice of different genetic backgrounds within a single U.S. research institute. PLoS ONE 6: e21435.
[21]
Bok K, Prikhodko VG, Green KY, Sosnovtsev SV (2009) Apoptosis in murine norovirus-infected RAW264.7 cells is associated with downregulation of survivin. J Virol 83: 3647–3656.
[22]
Gerondopoulos A, Jackson T, Monaghan P, Doyle N, Roberts LO (2010) Murine norovirus-1 cell entry is mediated through a non-clathrin-, non-caveolae-, dynamin- and cholesterol-dependent pathway. J Gen Virol 91: 1428–1438.
[23]
LoBue AD, Thompson JM, Lindesmith L, Johnston RE, Baric RS (2009) Alphavirus-adjuvanted norovirus-like particle vaccines: heterologous, humoral, and mucosal immune responses protect against murine norovirus challenge. J Virol 83: 3212–3227.
[24]
LoBue AD, Lindesmith LC, Baric RS (2010) Identification of cross-reactive norovirus CD4+ T cell epitopes. J Virol 84: 8530–8538.
[25]
Perry JW, Wobus CE (2010) Endocytosis of murine norovirus 1 into murine macrophages is dependent on dynamin II and cholesterol. J Virol 84: 6163–6176.
[26]
Taube S, Perry JW, Yetming K, Patel SP, Auble H, et al. (2009) Ganglioside-linked terminal sialic acid moieties on murine macrophages function as attachment receptors for murine noroviruses. J Virol 83: 4092–4101.
[27]
Farkas T, Dufour J, Jiang X, Sestak K (2010) Detection of norovirus-, sapovirus- and rhesus enteric calicivirus-specific antibodies in captive juvenile macaques. J Gen Virol 91: 734–738.
[28]
Wei C, Farkas T, Sestak K, Jiang X (2008) Recovery of infectious virus by transfection of in vitro-generated RNA from tulane calicivirus cDNA. J Virol 82: 11429–11436.
[29]
Jiang B, McClure HM, Fankhauser RL, Monroe SS, Glass RI (2004) Prevalence of rotavirus and norovirus antibodies in non-human primates. J Med Primatol 33: 30–33.
[30]
Wang Y, Tu X, Humphrey C, McClure H, Jiang X, et al. (2007) Detection of viral agents in fecal specimens of monkeys with diarrhea. J Med Primatol 36: 101–107.
[31]
Bok K, Parra GI, Mitra T, Abente E, Shaver CK, et al. (2011) Chimpanzees as an animal model for human norovirus infection and vaccine development. Proc Natl Acad Sci U S A 108: 325–330.
[32]
Patel MM, Widdowson MA, Glass RI, Akazawa K, Vinje J, et al. (2008) Systematic literature review of role of noroviruses in sporadic gastroenteritis. Emerg Infect Dis 14: 1224–1231.
[33]
Kapikian AZ, Wyatt RG, Dolin R, Thornhill TS, Kalica AR, et al. (1972) Visualization by immune electron microscopy of a 27-nm particle associated with acute infectious nonbacterial gastroenteritis. J Virol 10: 1075–1081.
[34]
El-Kamary SS, Pasetti MF, Mendelman PM, Frey SE, Bernstein DI, et al. (2010) Adjuvanted intranasal Norwalk virus-like particle vaccine elicits antibodies and antibody-secreting cells that express homing receptors for mucosal and peripheral lymphoid tissues. J Infect Dis 202: 1649–1658.
[35]
Atmar RL, Bernstein DI, Harro CD, Al-Ibrahim MS, Chen WH, et al. (2011) Norovirus vaccine against experimental human Norwalk Virus illness. N Engl J Med 365: 2178–2187.
[36]
Smith AW, Skilling DE, Anderson MP, Benirschke K (1985) Isolation of primate calicivirus Pan paniscus type 1 from a douc langur (Pygathrix nemaeus l.). J Wildl Dis 21: 426–428.
[37]
Symes SJ, Gunesekere IC, Marshall JA, Wright PJ (2007) Norovirus mixed infections in an oyster-associated outbreak: an opportunity for recombination. Arch Virol 152: 1075–1086.
[38]
Bull RA, Tanaka MM, White PA (2007) Norovirus recombination. J Gen Virol 88: 3347–3359.
[39]
Kaplan JE, Gary GW, Baron RC, Singh N, Schonberger LB, et al. (1982) Epidemiology of Norwalk gastroenteritis and the role of Norwalk virus in outbreaks of acute nonbacterial gastroenteritis. Ann Intern Med 96: 756–761.
[40]
Yang SY, Hwang KP, Wu FT, Wu HS, Hsiung CA, et al. (2010) Epidemiology and clinical peculiarities of norovirus and rotavirus infection in hospitalized young children with acute diarrhea in Taiwan, 2009. J Microbiol Immunol Infect 43: 506–514.
[41]
Parrino TA, Schreiber DS, Trier JS, Kapikian AZ, Blacklow NR (1977) Clinical immunity in acute gastroenteritis caused by Norwalk agent. N Engl J Med 297: 86–89.
[42]
Wyatt RG, Dolin R, Blacklow NR, DuPont HL, Buscho RF, et al. (1974) Comparison of three agents of acute infectious nonbacterial gastroenteritis by cross-challenge in volunteers. J Infect Dis 129: 709–714.
[43]
Agus SG, Dolin R, Wyatt RG, Tousimis AJ, Northrup RS (1973) Acute infectious nonbacterial gastroenteritis: intestinal histopathology. Histologic and enzymatic alterations during illness produced by the Norwalk agent in man. Ann Intern Med 79: 18–25.
[44]
Dolin R, Levy AG, Wyatt RG, Thornhill TS, Gardner JD (1975) Viral gastroenteritis induced by the Hawaii agent. Jejunal histopathology and serologic response. Am J Med 59: 761–768.
[45]
Schreiber DS, Blacklow NR, Trier JS (1974) The small intestinal lesion induced by Hawaii agent acute infectious nonbacterial gastroenteritis. J Infect Dis 129: 705–708.
[46]
Otto PH, Clarke IN, Lambden PR, Salim O, Reetz J, et al. (2011) Infection of calves with bovine norovirus GIII.1 strain Jena virus: an experimental model to study the pathogenesis of norovirus infection. J Virol 85: 12013–12021.
[47]
Bailey D, Kaiser WJ, Hollinshead M, Moffat K, Chaundry Y, et al. (2010) Feline calicivirus p32, p39 and p30 proteins localize to the endoplasmic reticulum to initiate replication complex formation. J Gen Virol 91: 739–749.
[48]
Lay MK, Atmar RL, Guix S, Bharadwaj U, He H, et al. (2010) Norwalk virus does not replicate in human macrophages or dendritic cells derived from the peripheral blood of susceptible humans. Virology 406: 1–11.
[49]
Chan MC, Ho W, Sung JJ (2011) In vitro whole-virus binding of a norovirus genogroup II genotype 4 strain to cells of the lamina propria and Brunner's glands in the human duodenum. J Virol 85: 8427–8430.
[50]
Bjorck P, Kincade PW (1998) CD19+ pro-B cells can give rise to dendritic cells in vitro. J Immunol 161: 5795–5799.
[51]
Molica S, Datillo A, Mannella A, Levato D (1994) CD11c expression in B-cell chronic lymphocytic leukemia. A comparison of results obtained with different monoclonal antibodies. Haematologica 79: 452–455.
[52]
Postigo AA, Corbi AL, Sanchez-Madrid F, de Landazuri MO (1991) Regulated expression and function of CD11c/CD18 integrin on human B lymphocytes. Relation between attachment to fibrinogen and triggering of proliferation through CD11c/CD18. J Exp Med 174: 1313–1322.
[53]
Ehrhardt GR, Hijikata A, Kitamura H, Ohara O, Wang JY, et al. (2008) Discriminating gene expression profiles of memory B cell subpopulations. J Exp Med 205: 1807–1817.
[54]
Sestak K, Merritt CK, Borda J, Saylor E, Schwamberger SR, et al. (2003) Infectious agent and immune response characteristics of chronic enterocolitis in captive rhesus macaques. Infect Immun 71: 4079–86.
[55]
Sestak K, McNeal MM, Choi A, Cole MJ, Ramesh G, et al. (2004) Defining T-cell-mediated immune responses in rotavirus-infected juvenile rhesus macaques. J Virol 78: 10258–64.
[56]
Mazumdar K, Alvarez X, Borda JT, Dufour J, Martin E, et al. (2010) Visualization of transepithelial passage of the immunogenic 33-residue peptide from alpha-2 gliadin in gluten-sensitive macaques. PLoS One 5: e10228.
[57]
Ramesh G, Alvarez X, Borda JT, Aye PP, Lackner AA, et al. (2005) Visualizing cytokine-secreting cells in situ in the rhesus macaque model of chronic gut inflammation. Clin Diagn Lab Immunol 12: 192–197.
[58]
Vega E, Barclay L, Gregoricus N, Williams K, Lee D, et al. (2011) Novel surveillance network for norovirus gastroenteritis outbreaks, United States. Emerg Infect Dis 17: 1389–1395.
