Patterns of SIV coreceptor use / Aimee Edinger.

Format:

Book

Manuscript

Microformat

Thesis/Dissertation

Author/Creator:

Edinger, Aimee.

Contributor:

Doms, Robert W., advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Cell and molecular biology.

Cell and molecular biology--Penn dissertations.

Cell and Molecular Biology.

Academic Dissertations as Topic.

Medical Subjects:

Cell and Molecular Biology.

Academic Dissertations as Topic.

Local Subjects:

Penn dissertations--Cell and molecular biology.

Cell and molecular biology--Penn dissertations.

Physical Description:

xi, 134 pages : illustrations ; 29 cm

Production:

1999.

Summary:

In 1996, chemokine receptors were shown to serve as coreceptors in HIV-1 infection. The role of chemokine receptors in SIV entry is investigated in this thesis. CCR5, but not CXCR4, was found to function as a coreceptor for both M- and T-tropic SIVs. However, Envs derived from M-tropic and T-tropic clones interacted with CCR5 differently, which may have implications for post-receptor signaling events. The influence of coreceptors other than CCR5 on SIV macrophage tropism was also evaluated. Many SIVs used GPR15 and STRL33 as coreceptors and several isolates used GPR1, ChemR23, CCR8, and APJ, but these coreceptors were not used as efficiently as CCR5 and their use did not correlate with tropism. One macrophage tropic isolate, SIV/17E-Fr, is also neurotropic and infects CD4-negative rhesus brain capillary endothelial cells (BCECs). Chemokine receptors were screened for potential primary receptor activity in this cell type. CCR5 served as a primary receptor for SIV/17E-Fr in BCECs, and a large number of SIV Env proteins used CCR5 as a primary receptor in vitro in cell-cell fusion and virus infection assays. When rhesus rather than human CCR5 was supplied, a wider variety of SIVs were capable of more efficient CD4-independent entry; the increased ability of Rh CCR5 to serve as a primary receptor was mapped to the N13D change in the N-terminus. CD4-independent Env proteins derived from SIV/17E-Fr and SIVsmDeltaB670 clone 3 were used in conjunction with a panel of CCR5/CCR2b chimeras and CCR5 point mutants to map residues involved in Env binding to CCR5. Molecules which function as coreceptors but not primary receptors likely disrupt Env-CCR5 binding. Several negatively charged residues in the N-terminus as well as Ser180 were identified as playing a role in CD4-independent infection and thus likely affect Env-CCR5 binding. The implications of these findings for viral tropism and pathogenesis are discussed within each chapter and are summarized in Chapter 6.

Notes:

Supervisor: Robert W. Doms.

Thesis (Ph.D. in Cell and Molecular Biology) -- University of Pennsylvania, 1999.

Includes bibliographical references.

Local Notes:

University Microfilms order no.: 99-26120.

OCLC:

187482378