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STRUCTURE-FUNCTION ANALYSIS OF THE VIRULENCE PROTEIN ICP34.5 FROM HERPES SIMPLEX VIRUS TYPE 2

Chatterjee, Somik
http://rave.ohiolink.edu/etdc/view?acc_num=kent1248108386

Abstract Details

2009, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
The ICP34.5 gene of herpes simplex virus (HSV) is diploid, has unusually high GC content and is expressed as a late protein in the viral cycle. The ICP34.5 protein is not essential for virus replication, but is essential for replication in neuronal and non-growing cells. The ICP34.5 protein from HSV-1 has an N-terminal arginine-rich region, a C-terminal mammalian GADD34-like region, and a central PAT (Proline-Alanine-Threonine) repeat region. The GADD34-like region of the HSV-2 ICP34.5 is almost identical to that of HSV-1, and the N-terminal region is also arginine-rich, although the protein sequence is considerably different elsewhere. The PAT repeat sequence is absent from HSV-2 ICP34.5, instead there is a 19 nucleotide repeat sequence in the ICP34.5 gene from HSV-2, which is excised as an intron. ICP34.5 from clinical sub-isolates of HSV-2 show extensive sequence homology with HSV-2 strain 333, but with a variable number of repeats of the 19 nucleotide sequence in the intron region. Differences in plaque morphology, efficiency of glycoprotein processing, and neuroinvasive disease potential of the virus are due to differences in the structure of ICP34.5 for HSV-1. My studies compared HSV type 1 and 2 variants of ICP34.5 with respect to structure and function. The HSV-2 strain 333 resembles the attenuated non-neuroinvasive HSV-1 strain KOS321 in that it forms large plaques in tissue culture cells, and glycoprotein processing is efficient. Cells expressing the ICP34.5 from HSV-2 strain 333 (by transfection) promoted full and efficient viral glycoprotein processing in cells infected with HSV-1 strain SP7. This shows that the ICP34.5 protein from HSV-2 strain 333, like the protein from HSV-1 KOS321, is sufficient to control and promote glycoprotein processing in HSV infected cells. However, unlike the KOS321 variant of ICP34.5, the HSV-2 strain 333 ICP34.5 protein localized in the cytoplasm rather than in the nucleus. Further studies show that the ICP34.5 from HSV-2 strain 333 binds to the mammalian autophagy protein beclin 1, as does the HSV-1 variants, despite considerable sequence differences. ICP34.5 proteins from HSV-2 and HSV-1, despite sequence differences, maintain the ability to bind to cellular proteins to enhance viral virulence.
Kenneth Rosenthal (Committee Chair)
176 p.
Biomedical Research
HSV-2; ICP34.5; structure-function; virulence

Recommended Citations

Citations

  • Chatterjee, S. (2009). STRUCTURE-FUNCTION ANALYSIS OF THE VIRULENCE PROTEIN ICP34.5 FROM HERPES SIMPLEX VIRUS TYPE 2 [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1248108386

    APA Style (7th edition)

  • Chatterjee, Somik. STRUCTURE-FUNCTION ANALYSIS OF THE VIRULENCE PROTEIN ICP34.5 FROM HERPES SIMPLEX VIRUS TYPE 2. 2009. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1248108386.

    MLA Style (8th edition)

  • Chatterjee, Somik. "STRUCTURE-FUNCTION ANALYSIS OF THE VIRULENCE PROTEIN ICP34.5 FROM HERPES SIMPLEX VIRUS TYPE 2." Doctoral dissertation, Kent State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=kent1248108386

    Chicago Manual of Style (17th edition)

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This open access ETD is published by Kent State University and OhioLINK.