Retroviral particle release.

Format:

Book

Thesis/Dissertation

Author/Creator:

Tanzi, Giancarlo Olivier.

Contributor:

Bates, Paul, advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Microbiology.

0410.

Penn dissertations--Cell and molecular biology.

Cell and molecular biology--Penn dissertations.

Local Subjects:

Penn dissertations--Cell and molecular biology.

Cell and molecular biology--Penn dissertations.

0410.

Physical Description:

149 pages

Contained In:

Dissertation Abstracts International 64-04B.

System Details:

Mode of access: World Wide Web.

text file

Summary:

Cellular release of retroviruses requires a membrane fission event. Gag polyprotein, the predominant retroviral structural protein, contains a "late domain" motif essential for efficient particle release. The late domain appears to often serve to recruit, either directly of indirectly, cellular Class E Vacuolar Protein Sorting (VPS) factors. Class E VPS factors normally function in protein trafficking events involving membrane fission and are presumably recruited to the site of particle budding to perform a similar reaction. This work sought to further understanding of the cellular and viral factors important to retroviral budding.

In Chapter 1, the Moloney Murine Leukemia Virus (M-MuLV) late domain is mapped to the Gag Pro Pro Pro Try sequence. A second putative M-MuLV late domain sequence, Pro Ser Ala Pro, is not required for efficient particle release. M-MuLV late domain mutants, like several late domain mutants described in the literature, exhibited multiple defects. Chapter 2 further examines these "secondary" late domain aberrations. While the Gag-Pol mutant (PPPY to PPPF or Y1 65F) was released at ∼10% of WT Gag-Pol levels, the particles released were unable to mediate infection. Y1 65F was determined to exhibit particle size aberrations and an inability to efficiently package Gag-Pol. These data, in conjunction with other published reports, suggests that retroviral late domain may be involved in processes beyond particle release.

The retrovirus Equine Infectious Anemia Virus (EIAV) Gag is unique in that is utilizes a Tyr Pro Asp Leu (YPDL) late domain sequence. Chapter 3 examines cellular factors involved in EIAV Gag release. The dominate negative class E VPS factor, VPS4, was utilized to demonstrate that EIAV Gag requires class E VPS components to complete particle release. However, RNA interference mediated knockdown of either TSG101, a VPS ESCRT-1 complex component or AP-2, a putative EIAV Gag late domain binding protein, caused no significant inhibition of EIAV Gag release. Thus while EIAV Gag egress utilizes class E VPS components, TSG101 and AP-2 do not appear essential in this process.

Notes:

Thesis (Ph.D. in Cell and Molecular Biology) -- University of Pennsylvania, 2003.

Source: Dissertation Abstracts International, Volume: 64-04, Section: B, page: 1613.

Adviser: Paul Bates.

Local Notes:

School code: 0175.

ISBN:

9780496352432

Access Restriction:

Restricted for use by site license.