This is a revised version of a competitive renewal application for continuing studies on HIV-1 infection in macrophages. The investigators have observed that nominally lymphotrophic (LT) viruses can infect macrophages which, in turn, can transmit the infection back to lymphocytes despite abnormal Gag-Pol processing of the LT virus produced in macrophages. A unique contract-dependent mechanism is proposed to account for this mode of transmission. In the proposal, Aim 1 will examine the structure, mode of entry, and cytopathic effects of LT virus transmitted from macrophages to T lymphocytes.
Aim 2 will employ alveolar macrophages (AM) from AIDS patients to test transmission and cytopathogenic activity for T lymphocytes. An attempt will be made to generate HVS-transformed AM capable of transmitting endogenous primary HIV-1.
Aim 3 will study the relative synthesis of Gag-Pol versus Gag, as well as intracellular localization and modification of Gag-Pol, and the localization of virion budding. Co-infection of monocyte-derived macrophages (MDM) with LT and MT viruses will test for protease dysfunction or inhibition Vaccinia virus vectors will be used to assess the role of ENV in regulating Gag-Pol expression in a virus-free system.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL043628-10
Application #
6125895
Study Section
Special Emphasis Panel (ZRG5-ARRA (03))
Project Start
1989-07-01
Project End
2000-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
10
Fiscal Year
2000
Total Cost
$254,815
Indirect Cost
Name
St. Luke's-Roosevelt Institute for Health Sciences
Department
Type
DUNS #
623216371
City
New York
State
NY
Country
United States
Zip Code
10019
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