The membrane glycoproteins specified by herpes simplex virus (HSV) are delivered to two locations within the cell following their synthesis. One is the plasma membrane and the other is the inner nuclear membrane where nucleocapsids acquire their envelopes. Virions initially containing immature glycoproteins are transported out of the cell via the Golgi apparatus. The research proposed here is directed toward answering the following questions: (1) What factors determine that the HSV glycoproteins will be delivered to the inner nuclear membrane? (2) What factors determine that the HSV glycoproteins will be incorporated in virions? Attention will focused on two of the HSV glycoproteins, designated gB and gE, and on G protein of vesicular stomatitis virus. Immunoelectron microscopy will be performed to assess the distribution of these glycoproteins in the membranes of transformed human cells that constitutively express a single viral glycoprotein. The cells will be infected with HSV mutants unable to produce gB or gE, in order to determine whether other HSV products influence the intracellular transport of gB or gE. Mutations will be introduced into the coding regions of gB and gE to define domains required for transport to the inner nuclear membrane, in infected or uninfected cells, and domains required for incorporation into virions. These experiments should yield new information about the intracellular transport and sorting of membrane proteins, addressing problems that have been relatively intractible until now. In addition, the results should contribute to an understanding of processes essential for HSV replication.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA021776-17
Application #
3481891
Study Section
Special Emphasis Panel (NSS)
Project Start
1977-09-01
Project End
1995-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
17
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Schools of Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Lajko, Michelle; Haddad, Alexander F; Robinson, Carolyn A et al. (2015) Using proximity biotinylation to detect herpesvirus entry glycoprotein interactions: Limitations for integral membrane glycoproteins. J Virol Methods 221:81-9
Fan, Qing; Longnecker, Richard; Connolly, Sarah A (2015) A Functional Interaction between Herpes Simplex Virus 1 Glycoprotein gH/gL Domains I and II and gD Is Defined by Using Alphaherpesvirus gH and gL Chimeras. J Virol 89:7159-69
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