Rat cytomegalovirus infection depletes MHC II in bone marrow derived dendritic cells.
While cytomegalovirus (CMV) infects and replicates in a multitude of cell types, the ability of the virus to replicate in antigen presenting cells (APCs) is believed to play a critical role in the viral dissemination and latency. CMV infection of APCs and manipulation of their function are important areas of investigation. CMV down regulation of MHC II is reportedly mediated by the HCMV proteins US2, US3, UL83, UL111a (vIL10) or through the induction of cellular IL10. In this study, we demonstrate that rat CMV (RCMV) significantly reduces MHC II expression neither by mechanisms that do not involve orthologues of the known HCMV genes nor by an increase in cellular IL10. Rat bone marrow derived dendritic cells (BMDC) were highly susceptible to infection with RCMV and a recombinant RCMV expressing eGFP. RCMV infection of BMDCs depleted both surface and intracellular MHC II to nearly undetectable levels as well as reduced surface expression of MHC I. The effect on MHC II only occurred in the infected GFP positive cells and is mediated by an immediate early or early viral gene product. Furthermore, treatment of uninfected immature DCs with virus-free conditioned supernatants from infected cells failed to down regulate MHC II. RCMV depletion of MHC II was sensitive to treatment with lysosomal inhibitors but not proteasomal inhibitors suggesting that the mechanism of RCMV-mediated down regulation of MHC II occurs through endocytic degradation. Since RCMV does not encode homologues of US2, US3, UL83 or UL111a, these data indicate a novel mechanism for RCMV depletion of MHC II.
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA.
Carmen C
CC
Baca Jones
Craig N
CN
Kreklywich
Ilhem
I
Messaoudi
Jennifer
J
Vomaske
Erin
E
McCartney
Susan L
SL
Orloff
Jay A
JA
Nelson
Daniel N
DN
Streblow
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D003586:Cytomegalovirus Infections / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism* / Q000821:virology*; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000502:physiology; D005805:Genes, MHC Class I / Q000502:physiology; D005802:Genes, MHC Class II / Q000502:physiology*; D051381:Rats