The effects of viral proteins on macrophage function
The effects of viral proteins on macrophage function
It is believed that viral accessory proteins contribute to immune cell dysfunction by modulating host signaling pathways. HIV-1 infection leads to a generalised loss of immune function culminating in AIDS. Macrophages are primary targets for HIV infection, can serve as a reservoir of virus and are necessary for efficient immune responses including the clearance of many infections and organisms typified in the latter stages of AIDS. Here the effects of HIV-1 Nef and Tat has been examined, when expressed alone, on macrophage function.
In this study transient and stable transfection of RAW 264.7 macrophage cell line was an inducible Nef expression vector has been shown to induce AP-1 DNA binding and transcriptional activation of AP-1 responsive genes. AP-1 induction was linked to the Src family protein tyrosine kinase Hck and the MAPK pathway leading to increased c-Fos expression.
Stable transfectants of RAW 264.7 cells expressing HIV-1 Tat protein have been shown to attenuate IFNγ induced nitrite production and conditioned media from these cells can also attenuate IFNγ induced nitrite production. Using a newly developed co-culture system Tat protein causes dramatic neurotoxic effects on brain tissue, not directly but through interaction with RAW 264.7 cells.
This work has demonstrated a possible route to macrophage dysfunction via Nef interaction with Hck and Tat attenuation of IFNγ signalling. Macrophages expressing Tat or exposed to exogenous recombinant Tat protein cause extensive damage to brain tissue.
This study has expanded understanding of HIV-1 accessory protein interaction with macrophage cells which will prove pivotal in the search for treatment to prevent the progression from HIV infection to AIDS or the development of AIDS dementia. This study has also given insights into the function of macrophages and provides the basis of a more detailed study of signalling pathways in these cells which may prove useful in the study of other macrophage mediated diseases.
University of Southampton
Biggs, Thelma Elizabeth
c781946a-4ca9-4ee2-bcd1-0cd8a86dce90
1998
Biggs, Thelma Elizabeth
c781946a-4ca9-4ee2-bcd1-0cd8a86dce90
Biggs, Thelma Elizabeth
(1998)
The effects of viral proteins on macrophage function.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
It is believed that viral accessory proteins contribute to immune cell dysfunction by modulating host signaling pathways. HIV-1 infection leads to a generalised loss of immune function culminating in AIDS. Macrophages are primary targets for HIV infection, can serve as a reservoir of virus and are necessary for efficient immune responses including the clearance of many infections and organisms typified in the latter stages of AIDS. Here the effects of HIV-1 Nef and Tat has been examined, when expressed alone, on macrophage function.
In this study transient and stable transfection of RAW 264.7 macrophage cell line was an inducible Nef expression vector has been shown to induce AP-1 DNA binding and transcriptional activation of AP-1 responsive genes. AP-1 induction was linked to the Src family protein tyrosine kinase Hck and the MAPK pathway leading to increased c-Fos expression.
Stable transfectants of RAW 264.7 cells expressing HIV-1 Tat protein have been shown to attenuate IFNγ induced nitrite production and conditioned media from these cells can also attenuate IFNγ induced nitrite production. Using a newly developed co-culture system Tat protein causes dramatic neurotoxic effects on brain tissue, not directly but through interaction with RAW 264.7 cells.
This work has demonstrated a possible route to macrophage dysfunction via Nef interaction with Hck and Tat attenuation of IFNγ signalling. Macrophages expressing Tat or exposed to exogenous recombinant Tat protein cause extensive damage to brain tissue.
This study has expanded understanding of HIV-1 accessory protein interaction with macrophage cells which will prove pivotal in the search for treatment to prevent the progression from HIV infection to AIDS or the development of AIDS dementia. This study has also given insights into the function of macrophages and provides the basis of a more detailed study of signalling pathways in these cells which may prove useful in the study of other macrophage mediated diseases.
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Published date: 1998
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Local EPrints ID: 463599
URI: http://eprints.soton.ac.uk/id/eprint/463599
PURE UUID: dcdac3bb-88fa-459b-86df-6bb956c4006c
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Date deposited: 04 Jul 2022 20:54
Last modified: 23 Jul 2022 02:15
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Author:
Thelma Elizabeth Biggs
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