Alphaherpesvirus glycoprotein M causes the relocalization of plasma membrane proteins.
Herpesvirus glycoprotein M (gM) is a multiple-spanning integral membrane protein found within the envelope of mature herpesviruses and is conserved throughout the Herpesviridae. gM is defined as a non-essential glycoprotein in alphaherpesviruses and has been proposed as playing a role in controlling final envelopment in a late secretory-pathway compartment such as the trans-Golgi network (TGN). Additionally, gM proteins have been shown to inhibit cell-cell fusion in transfection-based assays by an as yet unclear mechanism. Here, the effect of pseudorabies virus (PRV) gM and the herpes simplex virus type 1 (HSV-1) gM/UL49A complex on the fusion events caused by the HSV-1 glycoproteins gB, gD, gH and gL was investigated. Fusion of cells expressing HSV-1 gB, gD, gH and gL was efficiently inhibited by both PRV gM and HSV-1 gM/UL49A. Furthermore, expression of PRV gM or HSV-1 gM/UL49A, which are themselves localized to the TGN, caused both gD and gH/L to be relocalized from the plasma membrane to a juxtanuclear compartment, suggesting that fusion inhibition is caused by the removal of 'fusion' proteins from the cell surface. The ability of gM to cause the relocalization of plasma membrane proteins was not restricted to HSV-1 glycoproteins, as other viral and non-viral proteins were also affected. These data suggest that herpesvirus gM (gM/N) can alter the membrane trafficking itineraries of a broad range of proteins and this may have multiple functions.
Crump
Colin M
CM
Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
Bruun
Birgitte
B
Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
Bell
Susanne
S
Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
Pomeranz
Lisa E
LE
Princeton University, 301 Schultz Laboratory, Washington Road, Princeton, NJ 08544, USA.
Minson
Tony
T
Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
Browne
Helena M
HM
Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
D018138:Alphaherpesvirinae / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002966:Clathrin / Q000502:physiology; D004705:Endocytosis; D018259:Herpesvirus 1, Human; D006801:Humans; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D021381:Protein Transport; D014759:Viral Envelope Proteins / Q000378:metabolism / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000502:physiology; D021601:trans-Golgi Network / Q000378:metabolism
D002966:Clathrin; D008565:Membrane Proteins; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; C044200:glycoprotein H, herpes simplex virus type 1; C097733:glycoprotein N, Pseudorabies virus; C076024:UL49A protein, Human herpesvirus 2