Autophagy enhances the presentation of endogenous viral antigens on MHC class I molecules during HSV-1 infection.
Viral proteins are usually processed by the 'classical' major histocompatibility complex (MHC) class I presentation pathway. Here we showed that although macrophages infected with herpes simplex virus type 1 (HSV-1) initially stimulated CD8(+) T cells by this pathway, a second pathway involving a vacuolar compartment was triggered later during infection. Morphological and functional analyses indicated that distinct forms of autophagy facilitated the presentation of HSV-1 antigens on MHC class I molecules. One form of autophagy involved a previously unknown type of autophagosome that originated from the nuclear envelope. Whereas interferon-gamma stimulated classical MHC class I presentation, fever-like hyperthermia and the pyrogenic cytokine interleukin 1beta activated autophagy and the vacuolar processing of viral peptides. Viral peptides in autophagosomes were further processed by the proteasome, which suggests a complex interaction between the vacuolar and MHC class I presentation pathways.
English
Luc
L
Département de Pathologie et Biologie Cellulaire, Université de Montréal, Succursale Centre-Ville, Montreal, Quebec, Canada.
Chemali
Magali
M
Duron
Johanne
J
Rondeau
Christiane
C
Laplante
Annie
A
Gingras
Diane
D
Alexander
Diane
D
Leib
David
D
Norbury
Christopher
C
Lippé
Roger
R
Desjardins
Michel
M
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D001343:Autophagy / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000821:virology; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010588:Phagosomes / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000276:immunology; D014617:Vacuoles / Q000276:immunology
D000956:Antigens, Viral; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D046988:Proteasome Endopeptidase Complex