Rotavirus viremia and extraintestinal viral infection in the neonatal rat model

被引:116
作者
Crawford, Sue E.
Patel, Dinesh G.
Cheng, Elly
Berkova, Zuzana
Hyser, Joseph M.
Ciarlet, Max
Finegold, Milton J.
Conner, Margaret E.
Estes, Mary K. [1 ]
机构
[1] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA
[3] Texas Childrens Hosp, Dept Pathol, Houston, TX 77030 USA
[4] Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA
[5] Merck & Co Inc, Clin Res Dept, Blue Bell, PA 19422 USA
关键词
D O I
10.1128/JVI.80.10.4820-4832.2006
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Rotaviruses infect mature, differentiated enterocytes of the small intestine and, by an unknown mechanism, escape the gastrointestinal tract and cause viremia. The neonatal rat model of rotavirus infection was used to determine the kinetics of viremia, spread, and pathology of rotavirus in extraintestinal organs. Five-day-old rat pups were inoculated intragastrically with an animal (RRV) or human (HALI 166) rotavirus or phosphate-buffered saline. Blood was collected from a subset of rat pups, and following perfusion to remove residual blood, organs were removed and homogenized to analyze rotavirus-specific antigen by enzyme-linked immunosorbent assay and infectious rotavirus by fluorescent focus assay or fixed in formalin for histology and immunohistochemistry. Viremia was detected following rotavirus infection with RRV and HAL1166. The RRV 50% antigenemia dose was 1.8 x 10(3) PFU, and the 50% diarrhea dose was 7.7 x 10(5) PFU, indicating that infection and viremia occurred in the absence of diarrhea and that detecting rotavirus antigen in the blood was a more sensitive measure of infection than diarrhea. Rotavirus antigens and infectious virus were detected in multiple organs (stomach, intestines, liver, lungs, spleen, kidneys, pancreas, thymus. and bladder). Histopathological changes due to rotavirus infection included acute inflammation of the portal tract and bile duct, microsteatosis, necrosis, and inflammatory cell infiltrates in the parenchymas of the liver and lungs. Colocalization of structural and nonstructural proteins with histopathology in the liver and lungs indicated that the histological changes observed were due to rotavirus infection and replication. Replicating rotavirus was also detected in macrophages in the lungs and blood vessels, indicating a possible mechanism of rotavirus dissemination. Extraintestinal infectious rotavirus, but not diarrhea, was observed in the presence of passively or actively acquired rotavirus-specific antibody. These findings alter the previously accepted concept of rotavirus pathogenesis to include not only gastroenteritis but also viremia, and they indicate that rotavirus could cause a broad array of systemic diseases in a number of different organs.
引用
收藏
页码:4820 / 4832
页数:13
相关论文
共 56 条
  • [41] Histologic distribution of fatal rotaviral pneumonitis: An immunohistochemical and RT in situ PCR analysis
    Nuovo, GJ
    Owor, G
    Andrew, T
    Magro, C
    [J]. DIAGNOSTIC MOLECULAR PATHOLOGY, 2002, 11 (03) : 140 - 145
  • [42] Pager C, 2000, S AFR MED J, V90, P364
  • [43] Progress in developing animal models for biliary atresia
    Petersen, C
    Kuske, M
    Bruns, E
    Biermanns, D
    von Wussow, P
    Mildenberger, H
    [J]. EUROPEAN JOURNAL OF PEDIATRIC SURGERY, 1998, 8 (03) : 137 - 141
  • [44] AEROSOL TRANSMISSION OF EXPERIMENTAL ROTAVIRUS INFECTION
    PRINCE, DS
    ASTRY, C
    VONDERFECHT, S
    JAKAB, G
    SHEN, FM
    YOLKEN, RH
    [J]. PEDIATRIC INFECTIOUS DISEASE JOURNAL, 1986, 5 (02) : 218 - 222
  • [45] Extended excretion of rotavirus after severe diarrhoea in young children
    Richardson, S
    Grimwood, K
    Gorrell, R
    Palombo, E
    Barnes, G
    Bishop, R
    [J]. LANCET, 1998, 351 (9119) : 1844 - 1848
  • [46] RIEPENHOFFTALTY M, 1993, PEDIATR RES, V33, P394
  • [47] Detection of group C rotavirus in infants with extrahepatic biliary atresia
    RiepenhoffTalty, M
    Gouvea, V
    Evans, MJ
    Svensson, L
    Hoffenberg, E
    Sokol, RJ
    Uhnoo, I
    Greenberg, SJ
    Schakel, K
    Zhaori, G
    Fitzgerald, J
    Chong, S
    ElYousef, M
    Nemeth, A
    Brown, M
    Piccoli, D
    Hyams, J
    Ruffin, D
    Rossi, T
    [J]. JOURNAL OF INFECTIOUS DISEASES, 1996, 174 (01) : 8 - 15
  • [48] DETECTION OF ROTAVIRUS IN RESPIRATORY SECRETIONS OF CHILDREN WITH PNEUMONIA
    SANTOSHAM, M
    YOLKEN, RH
    QUIROZ, E
    DILLMAN, L
    ORO, G
    REEVES, WC
    SACK, RB
    [J]. JOURNAL OF PEDIATRICS, 1983, 103 (04) : 583 - 585
  • [49] Encephalopathy associated with haemophagocytic lymphohistiocytosis following rotavirus infection
    Takahashi, S
    Oki, J
    Miyamoto, A
    Koyano, S
    Ito, K
    Azuma, H
    Okuno, A
    [J]. EUROPEAN JOURNAL OF PEDIATRICS, 1999, 158 (02) : 133 - 137
  • [50] EXTRAMUCOSAL SPREAD AND DEVELOPMENT OF HEPATITIS IN IMMUNODEFICIENT AND NORMAL MICE INFECTED WITH RHESUS ROTAVIRUS
    UHNOO, I
    RIEPENHOFFTALTY, M
    DHARAKUL, T
    CHEGAS, P
    FISHER, JE
    GREENBERG, HB
    OGRA, PL
    [J]. JOURNAL OF VIROLOGY, 1990, 64 (01) : 361 - 368