Structure-function studies of soluble forms of herpes simplex virus glycoprotein D / Anthony V. Nicola.

Format:

Book

Manuscript

Microformat

Thesis/Dissertation

Author/Creator:

Nicola, Anthony V. (Veterinary virologist)

Contributor:

Cohen, Gary H., advisor.

Eisenberg, Rosely J., advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Molecular biology.

Molecular biology--Penn dissertations.

Molecular Biology.

Academic Dissertations as Topic.

Medical Subjects:

Molecular Biology.

Academic Dissertations as Topic.

Local Subjects:

Penn dissertations--Molecular biology.

Molecular biology--Penn dissertations.

Physical Description:

xiii, 177 pages : illustrations ; 29 cm

Production:

1996.

Summary:

Glycoprotein D (gD) of herpes simplex virus (HSV) is essential for virus entry. Truncated gD lacking the transmembrane and cytoplasmic tail regions (gDt) blocks plaque formation which supports a receptor-binding role for gD. Our laboratory previously identified four regions of gD (regions I to IV) which are important for virus entry. I analyzed the structure and function of baculovirus-expressed, truncated forms of wild type gD from HSV-1 (gD-1(306t)) and HSV-2, and four mutants each having a mutation in one of the functional regions. Mutant proteins with insertions in regions I or II were most altered in structure and stability, while mutants with insertions in regions III or IV were less altered. Wild type gDt inhibited plaque formation and cell-to-cell transmission of HSV-1. The region I mutant did not inhibit HSV infection, suggesting that this region of gD may be necessary for inhibition. Surprisingly, the other three mutant proteins functioned in all functional assays indicating the ability of gD to inhibit infection does not correlate with its ability to initiate infection. The region IV mutant, gD-1($\Delta$290-299t), had an unexpected enhanced inhibitory effect on HSV infection. These results suggest gD has more than one functional domain.

HSV strains that were resistant to gD-mediated interference were also resistant to inhibition by gDt, suggesting a link between these two phenomena. The structure and function of gDt derived from the inhibition-resistant viruses rid1 and ANG were analyzed. gD-1(rid1t) and gD-1(ANGt) had a potent inhibitory effect on wild type strains of HSV, but surprisingly, little or no effect on their parental strains. The antigenic structures of gD-1(rid1t) and gD-1(ANGt) were divergent from wild type, yet similar to each other and to gD-1($\Delta$290-299t). Thus, three different forms of gD have common structural changes that correlate with enhanced inhibitory activity against HSV. I conclude that inhibition of HSV infectivity by soluble gD is influenced by the structure of the blocking gDt as well as the form of gD in the target virus.

Notes:

Advisers: Gary H. Cohen; Rosely J. Eisenberg.

Thesis (Ph.D. in Molecular Biology) -- University of Pennsylvania, 1996.

Includes bibliographical references.

Local Notes:

University Microfilms order no.: 97-12982.

OCLC:

187469542