TY - JOUR
T1 - Endosomal/lysosomal retention and degradation of major histocompatibility complex class I molecules is induced by Myxoma virus
AU - Zúñiga, Martha C.
AU - Wang, Hong
AU - Barry, Michele
AU - McFadden, Grant
N1 - Funding Information:
We thank G. George Capps, Manuel Osorio, and Luis P. Villarreal for helpful discussions; Roger D. Canales for technical assistance; Kevin Kane, Peter Parham, Hidde Ploegh, Michael Edidin, Tom Kindt, and Minoru Fukuda for antibodies; S. Dales for BGMK cells; Chuck Wilson for LIPOFECTIN; Bill Sullivan for use of the confocal microscope; George Capps for preparation of the figures; and George Capps and Jim Kent for careful reading of the manuscript. This work was supported by grants to M.C.Z. from the NSF (MCB-9096241-008) and the NIH (R01-AI39055-02) and to G.M. from the MRC and NCI of Canada. H.W. was supported in part by funds from the UC Systemwide Biotechnology Program. G.M. is a senior scientist of the MRC, and M.B. is a fellow of the Alberta Heritage Foundation for Medical Research.
PY - 1999/9/1
Y1 - 1999/9/1
N2 - The highly immunosuppressive leporipoxvirus myxoma, previously was shown to promote the loss of cell surface class I major histocompatibility complex (MHC l) molecules. Here, we show that myxoma virus induces the loss of both cell surface and intracellular post-Golgi, β2-microglobulin-associated MHC I. Myxoma-induced loss of these MHC I molecules is abrogated by vacuolar ATPase inhibitors, NH4Cl, and leupeptin. Furthermore, immunofluorescence microscopic studies reveal that in myxoma-infected cells, β2-microglobulin- associated MHC l accumulates in Lamp-1+ vesicular structures, suggesting that myxoma virus targets MHC I for degradation in late endosomes and/or lysosomes. These events are regulated by early gene product or products because they occur unabated in cells infected with myxoma virus in the presence of cytosine arabinoside, an inhibitor of DNA synthesis. Studies with baby green monkey kidney cells transfected with wild-type and tail-less forms of a mouse MHC I molecule, H-2L(d), indicate that the MHC I cytoplasmic tail is required for myxoma-induced localization in Lamp-1+ organelles. Myxoma- induced endocytosis and degradation of MHC I may provide the virus with a means of dispensing with cell surface MHC I molecules that were loaded with peptides derived from viral proteins synthesized early in infection.
AB - The highly immunosuppressive leporipoxvirus myxoma, previously was shown to promote the loss of cell surface class I major histocompatibility complex (MHC l) molecules. Here, we show that myxoma virus induces the loss of both cell surface and intracellular post-Golgi, β2-microglobulin-associated MHC I. Myxoma-induced loss of these MHC I molecules is abrogated by vacuolar ATPase inhibitors, NH4Cl, and leupeptin. Furthermore, immunofluorescence microscopic studies reveal that in myxoma-infected cells, β2-microglobulin- associated MHC l accumulates in Lamp-1+ vesicular structures, suggesting that myxoma virus targets MHC I for degradation in late endosomes and/or lysosomes. These events are regulated by early gene product or products because they occur unabated in cells infected with myxoma virus in the presence of cytosine arabinoside, an inhibitor of DNA synthesis. Studies with baby green monkey kidney cells transfected with wild-type and tail-less forms of a mouse MHC I molecule, H-2L(d), indicate that the MHC I cytoplasmic tail is required for myxoma-induced localization in Lamp-1+ organelles. Myxoma- induced endocytosis and degradation of MHC I may provide the virus with a means of dispensing with cell surface MHC I molecules that were loaded with peptides derived from viral proteins synthesized early in infection.
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U2 - 10.1006/viro.1999.9840
DO - 10.1006/viro.1999.9840
M3 - Article
C2 - 10497104
AN - SCOPUS:19244367349
SN - 0042-6822
VL - 261
SP - 180
EP - 192
JO - Virology
JF - Virology
IS - 2
ER -