The ER-lumenal domain of the HHV-7 immunoevasin U21 directs class I MHC molecules to lysosomes.
Like all members of the herpesvirus family, human herpesvirus-7 has evolved mechanisms to evade immune detection. The human herpesvirus-7 gene product U21 encodes an immunoevasin that binds to class I major histocompatibility complex molecules and diverts them to a lysosomal compartment. Here we show that the cytoplasmic tail of U21, although sufficient to sequester a heterologous membrane protein (CD4 chimera), has no effect on U21's ability to redirect class I major histocompatibility complex molecules to lysosomes. Instead, the ER-lumenal domain of U21 is sufficient to redirect class I major histocompatibility complex molecules to the lysosomal compartment. These observations demonstrate a novel viral immunoevasive mechanism for U21, and implicate the ER-lumenal domain of a type I transmembrane protein in lysosomal sorting.
Hudson
Amy W
AW
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA. ahudson@hms.harvard.edu
Blom
Daniël
D
Howley
Peter M
PM
Ploegh
Hidde L
HL
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry; D015704:CD4 Antigens / Q000096:biosynthesis / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005434:Flow Cytometry; D016199:Herpesvirus 7, Human / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007930:Leucine / Q000737:chemistry; D008247:Lysosomes / Q000378:metabolism*; D008358:Mannose / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D014764:Viral Proteins / Q000737:chemistry* / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; D034741:RNA, Small Interfering; C488324:U21 glycoprotein, human herpesvirus 7; D014764:Viral Proteins; D007930:Leucine; D008358:Mannose