Placental extravillous cytotrophoblasts persistently express class I major histocompatibility complex molecules after human cytomegalovirus infection.
Human cytomegalovirus (HCMV) downregulates the class I major histocompatibility complexes (MHCs), HLA-A and -B, in infected fibroblasts to escape from antigen-specific cytotoxic T lymphocytes. The HCMV genes responsible for the downregulation of MHCs are US2, US3, US6, and US11, which encode type I membrane proteins working at the endoplasmic reticulum (ER). However, it is largely unknown whether HCMV downregulates the class I MHC molecules in placental extravillous cytotrophoblasts (EVT), which express HLA-C, -E, and -G to protect a semiallogenic fetus from maternal natural killer (NK) cells at the fetomaternal interface. Here, we report that differentiated EVT prepared from human first-trimester chorionic villi persistently express class I MHC molecules upon HCMV infection. When these US proteins were expressed in uninfected EVT, they were localized at the ER in the entire cytoplasm. However, subsequent HCMV infection resulted in dissociation of these US proteins from the ER, which relocated toward the cell membrane. In fibroblasts, these US proteins were localized at the ER before and after HCMV infection. These results suggest that the US gene products are not integrated into ER of HCMV-infected EVT and fail to downregulate class I MHC molecules.
Terauchi
Masakazu
M
Department of Comprehensive Reproductive Medicine, Graduate School, Tokyo Medical and Dental University, Bunkyo, Tokyo 113-8510, Japan.
Koi
Hideki
H
Hayano
Chikako
C
Toyama-Sorimachi
Noriko
N
Karasuyama
Hajime
H
Yamanashi
Yuji
Y
Aso
Takeshi
T
Shirakata
Masaki
M
D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000821:virology; D003587:Cytomegalovirus / Q000235:genetics / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000821:virology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism* / Q000821:virology; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C074546:US11 protein, herpesvirus; C118670:US2 protein, Varicellovirus; C095111:US3 protein, cytomegalovirus; C432877:US6 protein, Human cytomegalovirus; D014759:Viral Envelope Proteins; D014764:Viral Proteins