An endoplasmic reticulum-retained herpes simplex virus glycoprotein H is absent from secreted virions: evidence for reenvelopment during egress.
Although it is generally accepted that one of the first steps of herpesvirus egress is the acquisition of an envelope by nucleocapsids budding into the inner nuclear membrane, later events in the pathway are not well understood. We tested the hypothesis that the virus then undergoes de-envelopment, followed by reenvelopment at membranes outside the endoplasmic reticulum (ER), by constructing a recombinant virus in which the expression of an essential glycoprotein, gH, is restricted to the inner nuclear membrane-ER by means of the ER retention motif, KKXX. This targeting signal conferred the predicted ER localization properties on gH in recombinant virus-infected cells, and gH and gL polypeptides failed to become processed to their mature forms. Cells infected with the recombinant virus released particles with 100-fold less infectivity than those released by cells infected with the wild-type parent virus, yet the number of enveloped virus particles released into the medium was unaltered. These particles contained normal amounts of gD and VP16 but did not contain detectable amounts of gH, and these data are consistent with a model of virus exit whereby naked nucleocapsids in the cytoplasm acquire their final envelope from a subcellular compartment other than the ER-inner nuclear membrane.
Browne
H
H
Division of Virology, Department of Pathology, University of Cambridge, United Kingdom.
Bell
S
S
Minson
T
T
Wilson
D W
DW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D017931:DNA Primers; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000821:virology*; D015870:Gene Expression; D015726:Giant Cells / Q000821:virology; D018259:Herpesvirus 1, Human / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion; D019065:Virus Assembly / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C044200:glycoprotein H, herpes simplex virus type 1