Immunization with baculovirus-expressed recombinant rotavirus proteins VP1, VP4, VP6, and VP7 induces CD8+ T lymphocytes that mediate clearance of chronic rotavirus infection in SCID mice.
Clearance of chronic murine rotavirus infection in SCID mice can be demonstrated by adoptive transfer of immune CD8+ T lymphocytes from histocompatible donor mice immunized with a murine homotypic rotavirus (T. Dharakul, L. Rott, and H.B. Greenberg, J. Virol 64:4375-4382, 1990). The present study focuses on the protein specificity and heterotypic nature of cell-mediated clearance of chronic murine rotavirus infection in SCID mice. Heterotypic cell-mediated clearance was demonstrated in SCID mice infected with EDIM (murine) rotavirus after adoptive transfer of CD8+ T lymphocytes from BALB/c mice that were immunized with a variety of heterologous (nonmurine) rotaviruses including Wa (human, serotype 1), SA11 and RRV (simian, serotype 3), and NCDV and RF (bovine, serotype 6). This finding indicates the serotypic independence of T-cell-mediated rotavirus clearance. To further identify the rotavirus proteins that are capable of generating CD8+ T cells that mediate virus clearance, donor mice were immunized with SF-9 cells infected with a baculovirus recombinant expressing one of the following rotavirus proteins: VP1, VP2, NS53 (from RF), VP4, VP7, NS35 (from RRV), VP6, and NS28 (from SA11). SCID mice stopped shedding rotavirus after receiving CD8+ T cells from mice immunized with VP1, VP4, VP6, and VP7 but not with VP2, NS53, NS35, NS28, or wild-type baculovirus. These results suggest that heterotypic cell-mediated clearance of rotavirus in SCID mice is mediated by three of the major rotavirus structural proteins and by a putative polymerase protein.
Dharakul
T
T
Department of Medicine, Stanford University, California 94305-5100.
Labbe
M
M
Cohen
J
J
Bellamy
A R
AR
Street
J E
JE
Mackow
E R
ER
Fiore
L
L
Rott
L
L
Greenberg
H B
HB
D000818:Animals; D000956:Antigens, Viral; D016367:Baculoviridae / Q000235:genetics*; D016827:CD8 Antigens / Q000032:analysis / Q000276:immunology*; D002213:Capsid / Q000235:genetics / Q000276:immunology*; D036022:Capsid Proteins; D007111:Immunity, Cellular; D007114:Immunization; D016219:Immunotherapy, Adoptive; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012401:Rotavirus / Q000235:genetics / Q000276:immunology*; D012400:Rotavirus Infections / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013997:Time Factors
D000956:Antigens, Viral; D016827:CD8 Antigens; D036022:Capsid Proteins; D011994:Recombinant Proteins; C060339:VP4 protein, Rotavirus; C061332:VP6 protein, Rotavirus; C050779:VP7 protein, Rotavirus