Cutting edge: recombinant adenoviruses induce CD8 T cell responses to an inserted protein whose expression is limited to nonimmune cells.
CD8 T cells (T(CD8+)) play a crucial role in immunity to viruses. Current understanding of activation of naive T cells entails Ag presentation by professional APCs (pAPCs). What happens, however, when viruses evolve to avoid infecting pAPCs? We have studied the consequences of this strategy by generating recombinant adenoviruses that express influenza A virus nucleoprotein under the control of tissue-specific promoters. We show that the immunogenicity of such viruses requires their delivery to organs capable of expressing nucleoprotein. This indicates that infection of pAPCs is not required for adenoviruses to elicit a T(CD8+) response, probably due to a cross-priming via pAPCs. While this bodes well for recombinant adenoviruses as vaccines, it dims their prospects as gene therapy vectors.
Prasad
S A
SA
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Norbury
C C
CC
Chen
W
W
Bennink
J R
JR
Yewdell
J W
JW
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000276:immunology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology / Q000821:virology; D016601:RNA-Binding Proteins; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000821:virology; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins