Primary sequence domains required for the retention of rotavirus VP7 in the endoplasmic reticulum

p ROTEINS are targeted to various intracellular organelles with a high degree of specificity determined in part by primary sequence information in proteins of mitochondria (32) , the nucleus (14) , or those translocated into the endoplasmic reticulum (ER) ~ (3) . For several lumenal ER proteins, the sequence 'KDEL' at the carboxy terminus is necessary for their ER retention (4, 20, 24, 25) whereas ER specific retention sequence(s) have not been demonstrated for ER membrane-associated proteins. Viral protein expression systems have been useful for elucidating targeting behavior of proteins to the plasma membrane (1, 7, 9) or Golgi apparatus (21) . Rotavirus provides a similarly useful model system for investigating membrane-associated proteins targeted to the ER. During the maturation of rotavirus, virus cores assemble in cytoplasmic viroplasm structures, subsequently bud through the membranes of the rough ER or nuclear envelope and acquire a transient membrane envelope (8, 28, 29) . The mature double-capsid nonenveloped virions accumulate in the ER lumen. The structural glycoprotein and major neutralizing antigen VP7, is initially a membrane-associated protein with a lumenal orientation (13) . VP7 exhibits only a high-mannose tbrm of carbohydrate (13) consistent with its location solely in the ER (28, 29) . It is not known how VP7 assembles into virus particles nor by what mechanism the membrane elements are removed during virus maturation.