The U24 protein from human herpesvirus 6 and 7 affects endocytic recycling.
Modulation of T-cell receptor expression and signaling is essential to the survival of many viruses. The U24 protein expressed by human herpesvirus 6A, a ubiquitous human pathogen, has been previously shown to downregulate the T-cell receptor. Here, we show that U24 also mediates cell surface downregulation of a canonical early endosomal recycling receptor, the transferrin receptor, indicating that this viral protein acts by blocking early endosomal recycling. We present evidence that U24 is a C-tail-anchored protein that is dependent for its function on TRC40/Asna-1, a component of a posttranslational membrane insertion pathway. Finally, we find that U24 proteins from other roseoloviruses have a similar genetic organization and a conserved function that is dependent on a proline-rich motif. Inhibition of a basic cellular process by U24 has interesting implications not only for the pathogenicity of roseoloviruses but also for our understanding of the biology of endosomal transport.
Sullivan
Brian M
BM
Department of Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, 142 Life Sciences Addition, Berkeley, CA 94720, USA.
Coscoy
Laurent
L
D000595:Amino Acid Sequence; D015153:Blotting, Western; D002460:Cell Line; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis / Q000502:physiology*; D015654:Herpesvirus 6, Human / Q000378:metabolism*; D016199:Herpesvirus 7, Human / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011990:Receptors, Transferrin / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000737:chemistry / Q000502:physiology*
D011990:Receptors, Transferrin; D014764:Viral Proteins