Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 180-192 |
| Number of pages | 13 |
| Journal | Virology |
| Volume | 261 |
| Issue number | 2 |
| DOIs | |
| State | Published - Sep 1 1999 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Virology
Cite this
Endosomal/lysosomal retention and degradation of major histocompatibility complex class I molecules is induced by Myxoma virus. / Zúñiga, Martha C.; Wang, Hong; Barry, Michele; McFadden, Douglas.
In: Virology, Vol. 261, No. 2, 01.09.1999, p. 180-192.Research output: Contribution to journal › Article
}
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, Douglas
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
VL - 261
SP - 180
EP - 192
JO - Virology
JF - Virology
SN - 0042-6822
IS - 2
ER -