Chapter 36 : Rotaviruses

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Acute infectious diarrhea is one of the two most frequent diseases of young children. Until the early 1970s, numerous unsuccessful attempts were made to grow viral agents responsible for acute infectious diarrhea of children. The etiologic agent of epizootic diarrhea of infant mice (EDIM) was identified by electron microscopy in 1963 (1). Nonetheless, it was only with the discovery of the virus responsible for calf scours (with this same approach) in 1969 by Mebus et al (2) and of the human Norwalk virus by Kapikian et al (3) in 1972 that the methodology for identification of the viruses responsible for severe diarrhea in children was established. Using electron microscopy, Bishop et al (4) identified the first human rotavirus in an intestinal biopsy from a child with diarrhea. At roughly the same time, other groups used immune electron microscopy to identify the enteric caliciviruses and astroviruses, viruses that were also difficult to grow , as additional causes of acute infectious diarrhea in children and adults. Shortly after the discovery of human rotaviruses, it was realized that the EDIM virus and the calf scours virus were morphologically and antigenically related, and all these strains were grouped in the genus rotavirus. In rapid order, rotaviruses were shown to be among the most important pathogens of acute diarrhea in the young of many animals, including humans.

Citation: Franco M, Angel J, Greenberg H. 2017. Rotaviruses, p 853-872. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch36
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Image of FIGURE 1

Map of the world showing rotavirus mortality in 2008, reproduced with permission from ( ).

Citation: Franco M, Angel J, Greenberg H. 2017. Rotaviruses, p 853-872. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch36
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Image of FIGURE 2

Computer image reconstruction of a rotavirus triple-layered particle based on cryoelectronmicroscopy. VP4, the spike protein, and VP7 compose the outer viral layer, in the cutaway, the middle layer is composed of VP6 and inside this layer, the core (that contains VP1 and VP3 and the viral RNA not seen) formed by VP2 can be seen. [Image courtesy of Mark Yeager and reproduced with permission from ( )].

Citation: Franco M, Angel J, Greenberg H. 2017. Rotaviruses, p 853-872. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch36
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Image of FIGURE 3

Schematic representation of the rotavirus replication cycle in intestinal polarized epithelial cells. The initial cell attachment step involves binding to cellular glycans and subsequent interactions with multiple receptors/coreceptors mediated by VP8* and VP5*, respectively ( ). As a second step in entry, RVA have been proposed to interact with integrins α2β1, αVβ3, and αXβ2 and with the heat shock cognate protein hsc70 ( ). Although not completely established, most studies suggest that rotaviruses enter cells by endocytosis ( ) and then lose VP7 and VP4 ( ). In the cytoplasm, double-layered particles gain transcriptase activity and begin to synthesize viral mRNAs. Viral proteins accumulate in the cytoplasm in an electron-dense region called the viroplasm, where the viral genome is replicated and the assembly of progeny double-layered particles takes place ( ). An initial stage in viral assembly that is incompletely understood involves the assortment of single-stranded positive RNA strands corresponding to each one of the 11 gene segments ( ). A viral intermediate particle that consists of VP1, VP2, VP3, and probably all the nonstructural proteins, except NSP4, is then formed ( ). This complex acquires VP6 and during this process the nonstructural proteins are lost. Subsequently, the double-layered particles via VP6 interact with NSP4 that has been synthesized by ER ribosomes ( ). This interaction leads to budding of the double-layered particles (DLP) into the ER lumen. In this organelle the particles acquire a transient lipid membrane. Subsequently the viral particles acquire VP7 and VP4 and lose the transient enveloping membrane. The exit of the mature triple-layered viral particles from the ER and the cell has been incompletely elucidated and may involve a raft-dependent pathway before cell lysis occurs ( ) or may be a postlysis event. The mechanism of cell death induced by rotavirus (before or after viral exit) is incompletely understood but is dependent on cell apoptosis and in mice ( ).

Citation: Franco M, Angel J, Greenberg H. 2017. Rotaviruses, p 853-872. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch36
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Image of FIGURE 4

Cross-section of the small bowel villi from a rotavirus-infected mouse immunostained for rotavirus antigen. Note the restriction of growth of rotavirus to the mature villus tip cells of the small bowel.

Citation: Franco M, Angel J, Greenberg H. 2017. Rotaviruses, p 853-872. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch36
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1. Adams WR, Kraft LM . 1963. Epizootic diarrhea of infant mice: indentification of the etiologic agent. Science 141 : 359 360.[PubMed]
2. Mebus CA, Underdahl NR, Rhodes MB, Twiehaus MJ . 1969. Calf diarrhea (Scours): reproduced with a virus from a field outbreak. Univ Nebr Res Bull 233 : 1 16.
3. Kapikian AZ, Wyatt RG, Dolin R, Thornhill TS, Kalica AR, Chanock RM . 1972. Visualization by immune electron microscopy of a 27-nm particle associated with acute infectious nonbacterial gastroenteritis. J Virol 10 : 1075 1081.[PubMed]
4. Bishop RF, Davidson GP, Holmes IH, Ruck BJ . 1973. Virus particles in epithelial cells of duodenal mucosa from children with acute non-bacterial gastroenteritis. Lancet 302 : 1281 1283.[PubMed]
5. Tate JE, Burton AH, Boschi-Pinto C, Steele AD, Duque J, Parashar UD Network WH-cGRS. 2012. 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis 12 : 136 141.
6. Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, Faruque AS, Zaidi AK, Saha D, Alonso PL, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ochieng JB, Omore R, Oundo JO, Hossain A, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Hossain MJ, Akinsola A, Mandomando I, Nhampossa T, Acácio S, Biswas K, O'Reilly CE, Mintz ED, Berkeley LY, Muhsen K, Sommerfelt H, Robins-Browne RM, Levine MM . 2013. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382 : 209 222.
7. Leshem E, Moritz RE, Curns AT, Zhou F, Tate JE, Lopman BA, Parashar UD . 2014. Rotavirus vaccines and health care utilization for diarrhea in the United States (2007–2011). Pediatrics 134 : 15 23.[PubMed]
8. Tate JE, Haynes A, Payne DC, Cortese MM, Lopman BA, Patel MM, Parashar UD . 2013. Trends in national rotavirus activity before and after introduction of rotavirus vaccine into the national immunization program in the United States, 2000 to 2012. Pediatr Infect Dis J 32 : 741 744.[PubMed]
9. Payne DC, Vinjé J, Szilagyi PG, Edwards KM, Staat MA, Weinberg GA, Hall CB, Chappell J, Bernstein DI, Curns AT, Wikswo M, Shirley SH, Hall AJ, Lopman B, Parashar UD . 2013. Norovirus and medically attended gastroenteritis in U.S. children. N Engl J Med 368 : 1121 1130.[PubMed]
10. Bucardo F, Reyes Y, Svensson L, Nordgren J . 2014. Predominance of norovirus and sapovirus in Nicaragua after implementation of universal rotavirus vaccination. PLoS One 9 : e98201.[PubMed]
11. Estes MK, Greenberg HB, . 2013. Rotaviruses, p 1347 1401. In Knipe DM, Howley PM, Cohen JI, Griffin DE, Lamb RA, Martin MA, Racaniello VR, Roizman B (ed), Fields Virology, 6th ed, vol 2. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia.
12. Barman P, Ghosh S, Samajdar S, Mitra U, Dutta P, Bhattacharya SK, Krishnan T, Kobayashi N, Naik TN . 2006. RT-PCR based diagnosis revealed importance of human group B rotavirus infection in childhood diarrhoea. J Clin Virol 36 : 222 227.[PubMed]
13. Saiada F, Rahman HN, Moni S, Karim MM, Pourkarim MR, Azim T, Rahman M . 2011. Clinical presentation and molecular characterization of group B rotaviruses in diarrhoea patients in Bangladesh. J Med Microbiol 60 : 529 536.[PubMed]
14. Iturriza-Gómara M, Clarke I, Desselberger U, Brown D I, Thomas D, Gray J . 2004. Seroepidemiology of group C rotavirus infection in England and Wales. Eur J Epidemiol 19 : 589 595.[PubMed]
15. Mukhopadhya I, Anbu D, Iturriza-Gomara M, Gray JJ, Brown DW, Kavanagh O, Estes MK, Kang G . 2010. Anti-VP6 IgG antibodies against group A and group C rotaviruses in South India. Epidemiol Infect 138 : 442 447.[PubMed]
16. Sereno MM, Gorziglia MI . 1994. The outer capsid protein VP4 of murine rotavirus strain Eb represents a tentative new P type. Virology 199 : 500 504.[PubMed]
17. Dóró R, László B, Martella V, Leshem E, Gentsch J, Parashar U, Bányai K . 2014. Review of global rotavirus strain prevalence data from six years post vaccine licensure surveillance: is there evidence of strain selection from vaccine pressure? Infect Genet Evol 28 : 446 461.[PubMed]
18. Matthijnssens J, Ciarlet M, McDonald SM, Attoui H, Bányai K, Brister JR, Buesa J, Esona MD, Estes MK, Gentsch JR, Iturriza-Gómara M, Johne R, Kirkwood CD, Martella V, Mertens PP, Nakagomi O, Parreño V, Rahman M, Ruggeri FM, Saif LJ, Santos N, Steyer A, Taniguchi K, Patton JT, Desselberger U, Van Ranst M . 2011. Uniformity of rotavirus strain nomenclature proposed by the Rotavirus Classification Working Group (RCWG). Arch Virol 156 : 1397 1413.[PubMed]
19. Yeager M, Berriman JA, Baker TS, Bellamy AR . 1994. Three-dimensional structure of the rotavirus haemagglutinin VP4 by cryo-electron microscopy and difference map analysis. EMBO J 13 : 1011 1018.[PubMed]
20. Prasad BV, Rothnagel R, Zeng CQ, Jakana J, Lawton JA, Chiu W, Estes MK . 1996. Visualization of ordered genomic RNA and localization of transcriptional complexes in rotavirus. Nature 382 : 471 473.[PubMed]
21. Settembre EC, Chen JZ, Dormitzer PR, Grigorieff N, Harrison SC . 2011. Atomic model of an infectious rotavirus particle. EMBO J 30 : 408 416.[PubMed]
22. Trask SD, McDonald SM, Patton JT . 2012. Structural insights into the coupling of virion assembly and rotavirus replication. Nat Rev Microbiol 10 : 165 177.[PubMed]
23. Dormitzer PR, Nason EB, Prasad BV, Harrison SC . 2004. Structural rearrangements in the membrane penetration protein of a non-enveloped virus. Nature 430 : 1053 1058.[PubMed]
24. Yoder JD, Dormitzer PR . 2006. Alternative intermolecular contacts underlie the rotavirus VP5* two- to three-fold rearrangement. EMBO J 25 : 1559 1568.[PubMed]
25. Aoki ST, Settembre EC, Trask SD, Greenberg HB, Harrison SC, Dormitzer PR . 2009. Structure of rotavirus outer-layer protein VP7 bound with a neutralizing Fab. Science 324 : 1444 1447.[PubMed]
26. Abdelhakim AH, Salgado EN, Fu X, Pasham M, Nicastro D, Kirchhausen T, Harrison SC . 2014. Structural correlates of rotavirus cell entry. PLoS Pathog 10 : e1004355.[PubMed]
27. Estrozi LF, Settembre EC, Goret G, McClain B, Zhang X, Chen JZ, Grigorieff N, Harrison SC . 2013. Location of the dsRNA-dependent polymerase, VP1, in rotavirus particles. J Mol Biol 425 : 124 132.[PubMed]
28. Lawton JA, Estes MK, Prasad BV . 1999. Comparative structural analysis of transcriptionally competent and incompetent rotavirus-antibody complexes. Proc Natl Acad Sci USA 96 : 5428 5433.[PubMed]
29. Wood DJ, David TJ, Chrystie IL, Totterdell B . 1988. Chronic enteric virus infection in two T-cell immunodeficient children. J Med Virol 24 : 435 444.[PubMed]
30. Chen D, Luongo CL, Nibert ML, Patton JT . 1999. Rotavirus open cores catalyze 5′-capping and methylation of exogenous RNA: evidence that VP3 is a methyltransferase. Virology 265 : 120 130.[PubMed]
31. Zhang R, Jha BK, Ogden KM, Dong B, Zhao L, Elliott R, Patton JT, Silverman RH, Weiss SR . 2013. Homologous 2′,5′-phosphodiesterases from disparate RNA viruses antagonize antiviral innate immunity. Proc Natl Acad Sci USA 110 : 13114 13119.[PubMed]
32. Feng N, Yasukawa LL, Sen A, Greenberg HB . 2013. Permissive replication of homologous murine rotavirus in the mouse intestine is primarily regulated by VP4 and NSP1. J Virol 87 : 8307 8316.[PubMed]
33. Monnier N, Higo-Moriguchi K, Sun ZY, Prasad BV, Taniguchi K, Dormitzer PR . 2006. High-resolution molecular and antigen structure of the VP8* core of a sialic acid-independent human rotavirus strain. J Virol 80 : 1513 1523.[PubMed]
34. Arias CF, Silva-Ayala D, López S . 2015. Rotavirus entry: a deep journey into the cell with several exits. J Virol 89 : 890 893.[PubMed]
35. Golantsova NE, Gorbunova EE, Mackow ER . 2004. Discrete domains within the rotavirus VP5* direct peripheral membrane association and membrane permeability. J Virol 78 : 2037 2044.[PubMed]
36. Bican P, Cohen J, Charpilienne A, Scherrer R . 1982. Purification and characterization of bovine rotavirus cores. J Virol 43 : 1113 1117.[PubMed]
37. Aoki ST, Trask SD, Coulson BS, Greenberg HB, Dormitzer PR, Harrison SC . 2011. Cross-linking of rotavirus outer capsid protein VP7 by antibodies or disulfides inhibits viral entry. J Virol 85 : 10509 10517.[PubMed]
38. Sen A, Rott L, Phan N, Mukherjee G, Greenberg HB . 2014. Rotavirus NSP1 protein inhibits interferon-mediated STAT1 activation. J Virol 88 : 41 53.[PubMed]
39. Viskovska M, Anish R, Hu L, Chow DC, Hurwitz AM, Brown NG, Palzkill T, Estes MK, Prasad BV . 2014. Probing the sites of interactions of rotaviral proteins involved in replication. J Virol 88 : 12866 12881.[PubMed]
40. Piron M, Delaunay T, Grosclaude J, Poncet D . 1999. Identification of the RNA-binding, dimerization, and eIF4GI-binding domains of rotavirus nonstructural protein NSP3. J Virol 73 : 5411 5421.[PubMed]
41. Rubio RM, Mora SI, Romero P, Arias CF, López S . 2013. Rotavirus prevents the expression of host responses by blocking the nucleocytoplasmic transport of polyadenylated mRNAs. J Virol 87 : 6336 6345.[PubMed]
42. Gratia M, Sarot E, Vende P, Charpilienne A, Baron CH, Duarte M, Pyronnet S, Poncet D . 2015. Rotavirus NSP3 is a translational surrogate of the PABP-poly(A) complex. J Virol 89 : 8773 8782.
43. Ball JM, Tian P, Zeng CQ-Y, Morris AP, Estes MK . 1996. Age-dependent diarrhea induced by a rotaviral nonstructural glycoprotein. Science 272 : 101 104.[PubMed]
44. Storey SM, Gibbons TF, Williams CV, Parr RD, Schroeder F, Ball JM . 2007. Full-length, glycosylated NSP4 is localized to plasma membrane caveolae by a novel raft isolation technique. J Virol 81 : 5472 5483.[PubMed]
45. Tsugawa T, Tatsumi M, Tsutsumi H . 2014. Virulence-associated genome mutations of murine rotavirus identified by alternating serial passages in mice and cell cultures. J Virol 88 : 5543 5558.[PubMed]
46. Hoshino Y, Saif LJ, Kang SY, Sereno MM, Chen WK, Kapikian AZ . 1995. Identification of group A rotavirus genes associated with virulence of a porcine rotavirus and host range restriction of a human rotavirus in the gnotobiotic piglet model. Virology 209 : 274 280.[PubMed]
47. Venkataram Prasad BV, Shanker S, Hu L, Choi JM, Crawford SE, Ramani S, Czako R, Atmar RL, Estes MK . 2014. Structural basis of glycan interaction in gastroenteric viral pathogens. Curr Opin Virol 7 : 119 127.[PubMed]
48. Huang P, Xia M, Tan M, Zhong W, Wei C, Wang L, Morrow A, Jiang X . 2012. Spike protein VP8* of human rotavirus recognizes histo-blood group antigens in a type-specific manner. J Virol 86 : 4833 4843.[PubMed]
49. Hu L, Crawford SE, Czako R, Cortes-Penfield NW, Smith DF, Le Pendu J, Estes MK, Prasad BV . 2012. Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen. Nature 485 : 256 259.[PubMed]
50. Ramani S, Cortes-Penfield NW, Hu L, Crawford SE, Czako R, Smith DF, Kang G, Ramig RF, Le Pendu J, Prasad BV, Estes MK . 2013. The VP8* domain of neonatal rotavirus strain G10P[11] binds to type II precursor glycans. J Virol 87 : 7255 7264.[PubMed]
51. Matthijnssens J, De Grazia S, Piessens J, Heylen E, Zeller M, Giammanco GM, Bányai K, Buonavoglia C, Ciarlet M, Martella V, Van Ranst M . 2011. Multiple reassortment and interspecies transmission events contribute to the diversity of feline, canine and feline/canine-like human group A rotavirus strains. Infect Genet Evol 11 : 1396 1406.[PubMed]
52. Cuadras MA, Feigelstock DA, An S, Greenberg HB . 2002. Gene expression pattern in Caco-2 cells following rotavirus infection. J Virol 76 : 4467 4482.[PubMed]
53. Foulke-Abel J, In J, Kovbasnjuk O, Zachos NC, Ettayebi K, Blutt SE, Hyser JM, Zeng XL, Crawford SE, Broughman JR, Estes MK, Donowitz M . 2014. Human enteroids as an ex-vivo model of host-pathogen interactions in the gastrointestinal tract. Exp Biol Med (Maywood) 239 : 1124 1134.[PubMed]
54. Komoto S, Wakuda M, Ide T, Niimi G, Maeno Y, Higo-Moriguchi K, Taniguchi K . 2011. Modification of the trypsin cleavage site of rotavirus VP4 to a furin-sensitive form does not enhance replication efficiency. J Gen Virol 92 : 2914 2921.[PubMed]
55. Duponchel S, Troupin C, Vu LT, Schnuriger A, Trugnan G, Garbarg-Chenon A . 2014. Transfection of exogenous rotavirus rearranged RNA segments in cells infected with a WT rotavirus results in subsequent gene rearrangements. J Gen Virol 95 : 2089 2098.[PubMed]
56. Trask SD, Taraporewala ZF, Boehme KW, Dermody TS, Patton JT . 2010. Dual selection mechanisms drive efficient single-gene reverse genetics for rotavirus. Proc Natl Acad Sci USA 107 : 18652 18657.[PubMed]
57. Zambrano JL, Díaz Y, Peña F, Vizzi E, Ruiz MC, Michelangeli F, Liprandi F, Ludert JE . 2008. Silencing of rotavirus NSP4 or VP7 expression reduces alterations in Ca2+ homeostasis induced by infection of cultured cells. J Virol 82 : 5815 5824.[PubMed]
58. Bányai K, László B, Duque J, Steele AD, Nelson EA, Gentsch JR, Parashar UD . 2012. Systematic review of regional and temporal trends in global rotavirus strain diversity in the pre rotavirus vaccine era: insights for understanding the impact of rotavirus vaccination programs. Vaccine 30( Suppl 1) : A122 A130.[PubMed]
59. Velázquez FR, Matson DO, Calva JJ, Guerrero L, Morrow AL, Carter-Campbell S, Glass RI, Estes MK, Pickering LK, Ruiz-Palacios GM . 1996. Rotavirus infections in infants as protection against subsequent infections. N Engl J Med 335 : 1022 1028.[PubMed]
60. Cook SM, Glass RI, LeBaron CW, Ho MS . 1990. Global seasonality of rotavirus infections. Bull World Health Organ 68 : 171 177.[PubMed]
61. Turcios RM, Curns AT, Holman RC, Pandya-Smith I, LaMonte A, Bresee JS, Glass RI National Respiratory and Enteric Virus Surveillance System Collaborating Laboratories . 2006. Temporal and geographic trends of rotavirus activity in the United States, 1997–2004. Pediatr Infect Dis J 25 : 451 454.[PubMed]
62. Koopmans M, Brown D . 1999. Seasonality and diversity of Group A rotaviruses in Europe. Acta Paediatr Suppl 88( s426) : 14 19.[PubMed]
63. Pitzer VE, Viboud C, Simonsen L, Steiner C, Panozzo CA, Alonso WJ, Miller MA, Glass RI, Glasser JW, Parashar UD, Grenfell BT . 2009. Demographic variability, vaccination, and the spatiotemporal dynamics of rotavirus epidemics. Science 325 : 290 294.[PubMed]
64. Patel MM, Pitzer VE, Alonso WJ, Vera D, Lopman B, Tate J, Viboud C, Parashar UD . 2013. Global seasonality of rotavirus disease. Pediatr Infect Dis J 32 : e134 e14.[PubMed]
65. Bishop RF, Barnes GL, Cipriani E, Lund JS . 1983. Clinical immunity after neonatal rotavirus infection. A prospective longitudinal study in young children. N Engl J Med 309 : 72 76.[PubMed]
66. Vial PA, Kotloff KL, Losonsky GA . 1988. Molecular epidemiology of rotavirus infection in a room for convalescing newborns. J Infect Dis 157 : 668 673.[PubMed]
67. Kirkwood CD, Coulson BS, Bishop RF . 1996. G3P2 rotaviruses causing diarrhoeal disease in neonates differ in VP4, VP7 and NSP4 sequence from G3P2 strains causing asymptomatic neonatal infection. Arch Virol 141 : 1661 1676.[PubMed]
68. Rodriguez WJ, Kim HW, Brandt CD, Schwartz RH, Gardner MK, Jeffries B, Parrott RH, Kaslow RA, Smith JI, Kapikian AZ . 1987. Longitudinal study of rotavirus infection and gastroenteritis in families served by a pediatric medical practice: clinical and epidemiologic observations. Pediatr Infect Dis J 6 : 170 176.[PubMed]
69. Ward RL, Bernstein DI, Shukla R, Young EC, Sherwood JR, McNeal MM, Walker MC, Schiff GM . 1989. Effects of antibody to rotavirus on protection of adults challenged with a human rotavirus. J Infect Dis 159 : 79 88.[PubMed]
70. Lawrence J, He S, Martin J, Schödel F, Ciarlet M, Murray AV . 2014. Safety and immunogenicity of pentavalent rotavirus vaccine in a randomized, double-blind, placebo-controlled study in healthy elderly subjects. Hum Vaccin Immunother 10 : 2247 2254.[PubMed]
71. Dagan R, Bar-David Y, Sarov B, Katz M, Kassis I, Greenberg D, Glass RI, Margolis CZ, Sarov I . 1990. Rotavirus diarrhea in Jewish and Bedouin children in the Negev region of Israel: epidemiology, clinical aspects and possible role of malnutrition in severity of illness. Pediatr Infect Dis J 9 : 314 321.[PubMed]
72. Newman RD, Grupp-Phelan J, Shay DK, Davis RL . 1999. Perinatal risk factors for infant hospitalization with viral gastroenteritis. Pediatrics 103 : E3.[PubMed]
73. Cunliffe NA, Gondwe JS, Kirkwood CD, Graham SM, Nhlane NM, Thindwa BD, Dove W, Broadhead RL, Molyneux ME, Hart CA . 2001. Effect of concomitant HIV infection on presentation and outcome of rotavirus gastroenteritis in Malawian children. Lancet 358 : 550 555.[PubMed]
74. Gilger MA, Matson DO, Conner ME, Rosenblatt HM, Finegold MJ, Estes MK . 1992. Extraintestinal rotavirus infections in children with immunodeficiency. J Pediatr 120 : 912 917.[PubMed]
75. Dennehy PH, Cortese MM, Bégué RE, Jaeger JL, Roberts NE, Zhang R, Rhodes P, Gentsch J, Ward R, Bernstein DI, Vitek C, Bresee JS, Staat MA . 2006. A case-control study to determine risk factors for hospitalization for rotavirus gastroenteritis in U.S. children. Pediatr Infect Dis J 25 : 1123 1131.[PubMed]
76. Fischer TK, Viboud C, Parashar U, Malek M, Steiner C, Glass R, Simonsen L . 2007. Hospitalizations and deaths from diarrhea and rotavirus among children <5 years of age in the United States, 1993–2003. J Infect Dis 195 : 1117 1125.[PubMed]
77. Wobudeya E, Bachou H, Karamagi CK, Kalyango JN, Mutebi E, Wamani H . 2011. Breastfeeding and the risk of rotavirus diarrhea in hospitalized infants in Uganda: a matched case control study. BMC Pediatr 11 : 17.[PubMed]
78. Nordgren J, Sharma S, Bucardo F, Nasir W, Günaydın G, Ouermi D, Nitiema LW, Becker-Dreps S, Simpore J, Hammarström L, Larson G, Svensson L . 2014. Both Lewis and secretor status mediate susceptibility to rotavirus infections in a rotavirus genotype-dependent manner. Clin Infect Dis 59 : 1567 1573.[PubMed]
79. Imbert-Marcille BM, Barbé L, Dupé M, Le Moullac-Vaidye B, Besse B, Peltier C, Ruvoën-Clouet N, Le Pendu J . 2014. A FUT2 gene common polymorphism determines resistance to rotavirus A of the P[8] genotype. J Infect Dis 209 : 1227 1230.[PubMed]
80. Van Trang N, Vu HT, Le NT, Huang P, Jiang X, Anh DD . 2014. Association between norovirus and rotavirus infection and histo-blood group antigen types in Vietnamese children. J Clin Microbiol 52 : 1366 1374.[PubMed]
81. Gladstone BP, Ramani S, Mukhopadhya I, Muliyil J, Sarkar R, Rehman AM, Jaffar S, Gomara MI, Gray JJ, Brown DW, Desselberger U, Crawford SE, John J, Babji S, Estes MK, Kang G . 2011. Protective effect of natural rotavirus infection in an Indian birth cohort. N Engl J Med 365 : 337 346.[PubMed]
82. LeBaron CW, Lew J, Glass RI, Weber JM, Ruiz-Palacios GM Rotavirus Study Group . 1990. Annual rotavirus epidemic patterns in North America. Results of a 5-year retrospective survey of 88 centers in Canada, Mexico, and the United States. JAMA 264 : 983 988.[PubMed]
83. Azevedo MS, Yuan L, Jeong KI, Gonzalez A, Nguyen TV, Pouly S, Gochnauer M, Zhang W, Azevedo A, Saif LJ . 2005. Viremia and nasal and rectal shedding of rotavirus in gnotobiotic pigs inoculated with Wa human rotavirus. J Virol 79 : 5428 5436.[PubMed]
84. Le Guyader F, Haugarreau L, Miossec L, Dubois E, Pommepuy M . 2000. Three-year study to assess human enteric viruses in shellfish. Appl Environ Microbiol 66 : 3241 3248.[PubMed]
85. Butz AM, Fosarelli P, Dick J, Cusack T, Yolken R . 1993. Prevalence of rotavirus on high-risk fomites in day-care facilities. Pediatrics 92 : 202 205.[PubMed]
86. Widdowson MA, van Doornum GJ, van der Poel WH, de Boer AS, Mahdi U, Koopmans M . 2000. Emerging group-A rotavirus and a nosocomial outbreak of diarrhoea. Lancet 356 : 1161 1162.[PubMed]
87. Desikan P, Daniel JD, Kamalarathnam CN, Mathan MM . 1996. Molecular epidemiology of nosocomial rotavirus infection. J Diarrhoeal Dis Res 14 : 12 15.[PubMed]
88. Franco MA, Angel J, Greenberg HB . 2006. Immunity and correlates of protection for rotavirus vaccines. Vaccine 24 : 2718 2731.[PubMed]
89. Richardson S, Grimwood K, Gorrell R, Palombo E, Barnes G, Bishop R . 1998. Extended excretion of rotavirus after severe diarrhoea in young children. Lancet 351 : 1844 1848.[PubMed]
90. Torres-Medina A . 1984. Effect of rotavirus and/or Escherichia coli infection on the aggregated lymphoid follicles in the small intestine of neonatal gnotobiotic calves. Am J Vet Res 45 : 652 660.[PubMed]
91. Blutt SE, Kirkwood CD, Parreño V, Warfield KL, Ciarlet M, Estes MK, Bok K, Bishop RF, Conner ME . 2003. Rotavirus antigenaemia and viraemia: a common event? Lancet 362 : 1445 1449.[PubMed]
92. Ray P, Fenaux M, Sharma S, Malik J, Subodh S, Bhatnagar S, Greenberg H, Glass RI, Gentsch J, Bhan MK . 2006. Quantitative evaluation of rotaviral antigenemia in children with acute rotaviral diarrhea. J Infect Dis 194 : 588 593.[PubMed]
93. Blutt SE, Matson DO, Crawford SE, Staat MA, Azimi P, Bennett BL, Piedra PA, Conner ME . 2007. Rotavirus antigenemia in children is associated with viremia. PLoS Med 4 : e121.[PubMed]
94. Fenaux M, Cuadras MA, Feng N, Jaimes M, Greenberg HB . 2006. Extraintestinal spread and replication of a homologous EC rotavirus strain and a heterologous rhesus rotavirus in BALB/c mice. J Virol 80 : 5219 5232.[PubMed]
95. Greenberg HB, Clark HF, Offit PA . 1994. Rotavirus pathology and pathophysiology. Curr Top Microbiol Immunol 185 : 255 283.[PubMed]
96. Köhler T, Erben U, Wiedersberg H, Bannert N . 1990. [Histological findings of the small intestinal mucosa in rotavirus infections in infants and young children. Kinderarztl Prax 58 : 323 327.[PubMed]
97. Kang G, Iturriza-Gomara M, Wheeler JG, Crystal P, Monica B, Ramani S, Primrose B, Moses PD, Gallimore CI, Brown DW, Gray J . 2004. Quantitation of group A rotavirus by real-time reverse-transcription-polymerase chain reaction: correlation with clinical severity in children in South India. J Med Virol 73 : 118 122.[PubMed]
98. Noone C, Menzies IS, Banatvala JE, Scopes JW . 1986. Intestinal permeability and lactose hydrolysis in human rotaviral gastroenteritis assessed simultaneously by non-invasive differential sugar permeation. Eur J Clin Invest 16 : 217 225.
99. Batt RM, Embaye H, van de Waal S, Burgess D, Edwards GB, Hart CA . 1995. Application of organ culture of small intestine to the investigation of enterocyte damage by equine rotavirus. J Pediatr Gastroenterol Nutr 20 : 326 332.[PubMed]
100. Jourdan N, Brunet JP, Sapin C, Blais A, Cotte-Laffitte J, Forestier F, Quero AM, Trugnan G, Servin AL . 1998. Rotavirus infection reduces sucrase-isomaltase expression in human intestinal epithelial cells by perturbing protein targeting and organization of microvillar cytoskeleton. J Virol 72 : 7228 7236.[PubMed]
101. Zhang Y, Lee B, Thompson M, Glass R, Cama RI, Figueroa D, Gilman R, Taylor D, Stephenson C . 2000. Lactulose-mannitol intestinal permeability test in children with diarrhea caused by rotavirus and cryptosporidium. Diarrhea Working Group, Peru. J Pediatr Gastroenterol Nutr 31 : 16 21.
102. Stintzing G, Johansen K, Magnusson KE, Svensson L, Sundqvist T . 1986. Intestinal permeability in small children during and after rotavirus diarrhoea assessed with different-size polyethyleneglycols (PEG 400 and PEG 1000). Acta Paediatr Scand 75 : 1005 1009.[PubMed]
103. Obert G, Peiffer I, Servin AL . 2000. Rotavirus-induced structural and functional alterations in tight junctions of polarized intestinal Caco-2 cell monolayers. J Virol 74 : 4645 4651.[PubMed]
104. Istrate C, Hagbom M, Vikström E, Magnusson KE, Svensson L . 2014. Rotavirus infection increases intestinal motility but not permeability at the onset of diarrhea. J Virol 88 : 3161 3169.[PubMed]
105. Lundgren O, Peregrin AT, Persson K, Kordasti S, Uhnoo I, Svensson L . 2000. Role of the enteric nervous system in the fluid and electrolyte secretion of rotavirus diarrhea. Science 287 : 491 495.
106. Hagbom M, Istrate C, Engblom D, Karlsson T, Rodriguez-Diaz J, Buesa J, Taylor JA, Loitto VM, Magnusson KE, Ahlman H, Lundgren O, Svensson L . 2011. Rotavirus stimulates release of serotonin (5-HT) from human enterochromaffin cells and activates brain structures involved in nausea and vomiting. PLoS Pathog 7 : e1002115.[PubMed]
107. Salazar-Lindo E, Santisteban-Ponce J, Chea-Woo E, Gutierrez M . 2000. Racecadotril in the treatment of acute watery diarrhea in children. N Engl J Med 343 : 463 467.[PubMed]
108. Coulson BS, Grimwood K, Hudson IL, Barnes GL, Bishop RF . 1992. Role of coproantibody in clinical protection of children during reinfection with rotavirus. J Clin Microbiol 30 : 1678 1684.[PubMed]
109. Bass DM, Baylor M, Broome R, Greenberg HB . 1992. Molecular basis of age-dependent gastric inactivation of rhesus rotavirus in the mouse. J Clin Invest 89 : 1741 1745.[PubMed]
110. Newburg DS, Peterson JA, Ruiz-Palacios GM, Matson DO, Morrow AL, Shults J, Guerrero ML, Chaturvedi P, Newburg SO, Scallan CD, Taylor MR, Ceriani RL, Pickering LK . 1998. Role of human-milk lactadherin in protection against symptomatic rotavirus infection. Lancet 351 : 1160 1164.[PubMed]
111. Uchiyama R, Chassaing B, Zhang B, Gewirtz AT . 2014. Antibiotic treatment suppresses rotavirus infection and enhances specific humoral immunity. J Infect Dis 210 : 171 182.[PubMed]
112. Uchiyama R, Chassaing B, Zhang B, Gewirtz AT . 2015. MyD88-mediated TLR signaling protects against acute rotavirus infection while inflammasome cytokines direct Ab response. Innate Immun 21 : 416 428.[PubMed]
113. Rodríguez LS, Narváez CF, Rojas OL, Franco MA, Ángel J . 2012. Human myeloid dendritic cells treated with supernatants of rotavirus infected Caco-2 cells induce a poor Th1 response. Cell Immunol 272 : 154 161.[PubMed]
114. Barreto A, Rodríguez LS, Rojas OL, Wolf M, Greenberg HB, Franco MA, Angel J . 2010. Membrane vesicles released by intestinal epithelial cells infected with rotavirus inhibit T-cell function. Viral Immunol 23 : 595 608.[PubMed]
115. Barro M, Patton JT . 2005. Rotavirus nonstructural protein 1 subverts innate immune response by inducing degradation of IFN regulatory factor 3. Proc Natl Acad Sci USA 102 : 4114 4119.[PubMed]
116. Pott J, Mahlakõiv T, Mordstein M, Duerr CU, Michiels T, Stockinger S, Staeheli P, Hornef MW . 2011. IFN-lambda determines the intestinal epithelial antiviral host defense. Proc Natl Acad Sci USA 108 : 7944 7949.[PubMed]
117. De Boissieu D, Lebon P, Badoual J, Bompard Y, Dupont C . 1993. Rotavirus induces alpha-interferon release in children with gastroenteritis. J Pediatr Gastroenterol Nutr 16 : 29 32.[PubMed]
118. Hernández PP, Mahlakõiv T, Yang I, Schwierzeck V, Nguyen N, Guendel F, Gronke K, Ryffel B, Hölscher C, Dumoutier L, Renauld JC, Suerbaum S, Staeheli P, Diefenbach A . 2015. Interferon-λ and interleukin 22 act synergistically for the induction of interferon-stimulated genes and control of rotavirus infection. Nat Immunol 16 : 698 707.[PubMed]
119. Zhang B, Chassaing B, Shi Z, Uchiyama R, Zhang Z, Denning TL, Crawford SE, Pruijssers AJ, Iskarpatyoti JA, Estes MK, Dermody TS, Ouyang W, Williams IR, Vijay-Kumar M, Gewirtz AT . 2014. Viral infection. Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18. Science 346 : 861 865.[PubMed]
120. Jaimes MC, Feng N, Greenberg HB . 2005. Characterization of homologous and heterologous rotavirus-specific T-cell responses in infant and adult mice. J Virol 79 : 4568 4579.[PubMed]
121. VanCott JL, Prada AE, McNeal MM, Stone SC, Basu M, Huffer B Jr, Smiley KL, Shao M, Bean JA, Clements JD, Choi AH, Ward RL . 2006. Mice develop effective but delayed protective immune responses when immunized as neonates either intranasally with nonliving VP6/LT(R192G) or orally with live rhesus rotavirus vaccine candidates. J Virol 80 : 4949 4961.[PubMed]
122. Feng N, Jaimes MC, Lazarus NH, Monak D, Zhang C, Butcher EC, Greenberg HB . 2006. Redundant role of chemokines CCL25/TECK and CCL28/MEC in IgA+ plasmablast recruitment to the intestinal lamina propria after rotavirus infection. J Immunol 176 : 5749 5759.[PubMed]
123. Matson DO, O'Ryan ML, Herrera I, Pickering LK, Estes MK . 1993. Fecal antibody responses to symptomatic and asymptomatic rotavirus infections. J Infect Dis 167 : 577 583.[PubMed]
124. Grimwood K, Lund JC, Coulson BS, Hudson IL, Bishop RF, Barnes GL . 1988. Comparison of serum and mucosal antibody responses following severe acute rotavirus gastroenteritis in young children. J Clin Microbiol 26 : 732 738.[PubMed]
125. Coulson BS, Grimwood K, Masendycz PJ, Lund JS, Mermelstein N, Bishop RF, Barnes GL . 1990. Comparison of rotavirus immunoglobulin A coproconversion with other indices of rotavirus infection in a longitudinal study in childhood. J Clin Microbiol 28 : 1367 1374.[PubMed]
126. Johansen K, Granqvist L, Karlén K, Stintzing G, Uhnoo I, Svensson L . 1994. Serum IgA immune response to individual rotavirus polypeptides in young children with rotavirus infection. Arch Virol 138 : 247 259.[PubMed]
127. Angel J, Steele AD, Franco MA . 2014. Correlates of protection for rotavirus vaccines: possible alternative trial endpoints, opportunities, and challenges. Hum Vaccin Immunother 10 : 3659 3671.[PubMed]
128. Youngman KR, Franco MA, Kuklin NA, Rott LS, Butcher EC, Greenberg HB . 2002. Correlation of tissue distribution, developmental phenotype, and intestinal homing receptor expression of antigen-specific B cells during the murine anti-rotavirus immune response. J Immunol 168 : 2173 2181.[PubMed]
129. Jaimes MC, Rojas OL, Kunkel EJ, Lazarus NH, Soler D, Butcher EC, Bass D, Angel J, Franco MA, Greenberg HB . 2004. Maturation and trafficking markers on rotavirus-specific B cells during acute infection and convalescence in children. J Virol 78 : 10967 10976.[PubMed]
130. Parez N, Garbarg-Chenon A, Fourgeux C, Le Deist F, Servant-Delmas A, Charpilienne A, Cohen J, Schwartz-Cornil I . 2004. The VP6 protein of rotavirus interacts with a large fraction of human naive B cells via surface immunoglobulins. J Virol 78 : 12489 12496.[PubMed]
131. Weitkamp JH, Kallewaard NL, Bowen AL, Lafleur BJ, Greenberg HB, Crowe JE Jr . 2005. VH1-46 is the dominant immunoglobulin heavy chain gene segment in rotavirus-specific memory B cells expressing the intestinal homing receptor alpha4beta7. J Immunol 174 : 3454 3460.[PubMed]
132. Tian C, Luskin GK, Dischert KM, Higginbotham JN, Shepherd BE, Crowe JE Jr . 2008. Immunodominance of the VH1-46 antibody gene segment in the primary repertoire of human rotavirus-specific B cells is reduced in the memory compartment through somatic mutation of nondominant clones. J Immunol 180 : 3279 3288.[PubMed]
133. Herrera D, Rojas OL, Duarte-Rey C, Mantilla RD, Angel J, Franco MA . 2014. Simultaneous assessment of rotavirus-specific memory B cells and serological memory after B cell depletion therapy with rituximab. PLoS One 9 : e97087.[PubMed]
134. Nair N, Newell EW, Vollmers C, Quake SR, Morton JM, Davis MM, He XS, Greenberg HB . 2015. High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry. Mucosal Immunol.[PubMed]
135. Jaimes MC, Rojas OL, González AM, Cajiao I, Charpilienne A, Pothier P, Kohli E, Greenberg HB, Franco MA, Angel J . 2002. Frequencies of virus-specific CD4(+) and CD8(+) T lymphocytes secreting gamma interferon after acute natural rotavirus infection in children and adults. J Virol 76 : 4741 4749.[PubMed]
136. Rojas OL, González AM, González R, Pérez-Schael I, Greenberg HB, Franco MA, Angel J . 2003. Human rotavirus specific T cells: quantification by ELISPOT and expression of homing receptors on CD4+ T cells. Virology 314 : 671 679.[PubMed]
137. Narváez CF, Angel J, Franco MA . 2005. Interaction of rotavirus with human myeloid dendritic cells. J Virol 79 : 14526 14535.[PubMed]
138. Mesa MC, Gutiérrez L, Duarte-Rey C, Angel J, Franco MA . 2010. A TGF-β mediated regulatory mechanism modulates the T cell immune response to rotavirus in adults but not in children. Virology 399 : 77 86.[PubMed]
139. Parra M, Herrera D, Jácome MF, Mesa MC, Rodríguez LS, Guzmán C, Angel J, Franco MA . 2014. Circulating rotavirus-specific T cells have a poor functional profile. Virology 468-470C : 340 350.
140. Parra M, Herrera D, Calvo-Calle JM, Stern LJ, Parra-López CA, Butcher E, Franco M, Angel J . 2014. Circulating human rotavirus specific CD4 T cells identified with a class II tetramer express the intestinal homing receptors α4β7 and CCR9. Virology 452–453 : 191 201.[PubMed]
141. Burns JW, Siadat-Pajouh M, Krishnaney AA, Greenberg HB . 1996. Protective effect of rotavirus VP6-specific IgA monoclonal antibodies that lack neutralizing activity. Science 272 : 104 107.[PubMed]
142. Corthésy B, Benureau Y, Perrier C, Fourgeux C, Parez N, Greenberg H, Schwartz-Cornil I . 2006. Rotavirus anti-VP6 secretory immunoglobulin A contributes to protection via intracellular neutralization but not via immune exclusion. J Virol 80 : 10692 10699.[PubMed]
143. Yuan L, Honma S, Ishida S, Yan XY, Kapikian AZ, Hoshino Y . 2004. Species-specific but not genotype-specific primary and secondary isotype-specific NSP4 antibody responses in gnotobiotic calves and piglets infected with homologous host bovine (NSP4[A]) or porcine (NSP4[B]) rotavirus. Virology 330 : 92 104.[PubMed]
144. Velázquez FR, Matson DO, Guerrero ML, Shults J, Calva JJ, Morrow AL, Glass RI, Pickering LK, Ruiz-Palacios GM . 2000. Serum antibody as a marker of protection against natural rotavirus infection and disease. J Infect Dis 182 : 1602 1609.[PubMed]
145. Green KY, Taniguchi K, Mackow ER, Kapikian AZ . 1990. Homotypic and heterotypic epitope-specific antibody responses in adult and infant rotavirus vaccinees: implications for vaccine development. J Infect Dis 161 : 667 679.[PubMed]
146. Ward RL, Kirkwood CD, Sander DS, Smith VE, Shao M, Bean JA, Sack DA, Bernstein DI . 2006. Reductions in cross-neutralizing antibody responses in infants after attenuation of the human rotavirus vaccine candidate 89–12. J Infect Dis 194 : 1729 1736.[PubMed]
147. Cheuvart B, Neuzil KM, Steele AD, Cunliffe N, Madhi SA, Karkada N, Han HH, Vinals C . 2014. Association of serum anti-rotavirus immunoglobulin A antibody seropositivity and protection against severe rotavirus gastroenteritis: analysis of clinical trials of human rotavirus vaccine. Hum Vaccin Immunother 10 : 505 511.[PubMed]
148. Patel M, Glass RI, Jiang B, Santosham M, Lopman B, Parashar U . 2013. A systematic review of anti-rotavirus serum IgA antibody titer as a potential correlate of rotavirus vaccine efficacy. J Infect Dis 208 : 284 294.[PubMed]
149. Herrera D, Vásquez C, Corthésy B, Franco MA, Angel J . 2013. Rotavirus specific plasma secretory immunoglobulin in children with acute gastroenteritis and children vaccinated with an attenuated human rotavirus vaccine. Hum Vaccin Immunother 9 : 2409 2417.[PubMed]