HIV-1 transmission between T cells and macrophages: consequences for viral pathogenesis.
<p>Within the paradigm of HIV-1 infection, macrophages play a crucial role as long-lived viral reservoirs. However, cell-free virus infection is inefficient and is unlikely to explain the levels of infection observed <em>in vivo</em>. To investigate the hypothesis that macrophages...
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
2013
|
| Subjects: |
| _version_ | 1826315842571206656 |
|---|---|
| author | Baxter, A |
| author2 | Sattentau, Q |
| author_facet | Sattentau, Q Baxter, A |
| author_sort | Baxter, A |
| collection | OXFORD |
| description | <p>Within the paradigm of HIV-1 infection, macrophages play a crucial role as long-lived viral reservoirs. However, cell-free virus infection is inefficient and is unlikely to explain the levels of infection observed <em>in vivo</em>. To investigate the hypothesis that macrophages might be infected via direct contact with HIV-1-infected T cells, macrophage and HIV-1-infected T cell cocultures were imaged in real time. I observed that macrophages preferentially phagocytosed HIV-1-infected T cells and, using long-term culture assays, I established that following coculture the macrophage became productively infected. Phagocytosis of HIV-1-infected cells occurred independently of viral tropism; however, productive infection following T cell phagocytosis was restricted by viral tropism. Imaging flow cytometry showed that macrophages primarily phagocytose dying HIV-1-infected T cells. However, a significant population of HIV-1-infected 'healthy' cells were also taken up. Furthermore, ICAM-1 was identified as mediating the uptake of HIV-1-infected T cells. These results indicate that apoptosis plays a significant, but not sufficient, role in the mechanism for recognition and uptake of HIV-1-infected T cells.</p> <p>The response of macrophages to HIV-1 infection remains controversial. Using both primary macrophages and a monocyte/macrophage NFκB reporter line assay, I demonstrated that macrophages are activated in response to HIV-1-infected T cells. In addition, during coculture with HIV-1-infected T cells, macrophages upregulated secretion of Th1 cytokines, with associated dysregulation of regulatory cytokines. Finally, data presented suggest that polarisation of macrophages towards M1 and M2 phenotypes alters the susceptibility to HIV-1 infection in the cell-to-cell route.</p> |
| first_indexed | 2024-03-06T19:32:31Z |
| format | Thesis |
| id | oxford-uuid:1df105a3-1f0d-4159-8e01-3fdb231a0c42 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:33:35Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:1df105a3-1f0d-4159-8e01-3fdb231a0c422024-12-01T16:46:46ZHIV-1 transmission between T cells and macrophages: consequences for viral pathogenesis.Thesishttp://purl.org/coar/resource_type/c_db06uuid:1df105a3-1f0d-4159-8e01-3fdb231a0c42Infectious diseasesVirusesHIV/AIDSEnglishOxford University Research Archive - Valet2013Baxter, ASattentau, QMoore, R<p>Within the paradigm of HIV-1 infection, macrophages play a crucial role as long-lived viral reservoirs. However, cell-free virus infection is inefficient and is unlikely to explain the levels of infection observed <em>in vivo</em>. To investigate the hypothesis that macrophages might be infected via direct contact with HIV-1-infected T cells, macrophage and HIV-1-infected T cell cocultures were imaged in real time. I observed that macrophages preferentially phagocytosed HIV-1-infected T cells and, using long-term culture assays, I established that following coculture the macrophage became productively infected. Phagocytosis of HIV-1-infected cells occurred independently of viral tropism; however, productive infection following T cell phagocytosis was restricted by viral tropism. Imaging flow cytometry showed that macrophages primarily phagocytose dying HIV-1-infected T cells. However, a significant population of HIV-1-infected 'healthy' cells were also taken up. Furthermore, ICAM-1 was identified as mediating the uptake of HIV-1-infected T cells. These results indicate that apoptosis plays a significant, but not sufficient, role in the mechanism for recognition and uptake of HIV-1-infected T cells.</p> <p>The response of macrophages to HIV-1 infection remains controversial. Using both primary macrophages and a monocyte/macrophage NFκB reporter line assay, I demonstrated that macrophages are activated in response to HIV-1-infected T cells. In addition, during coculture with HIV-1-infected T cells, macrophages upregulated secretion of Th1 cytokines, with associated dysregulation of regulatory cytokines. Finally, data presented suggest that polarisation of macrophages towards M1 and M2 phenotypes alters the susceptibility to HIV-1 infection in the cell-to-cell route.</p> |
| spellingShingle | Infectious diseases Viruses HIV/AIDS Baxter, A HIV-1 transmission between T cells and macrophages: consequences for viral pathogenesis. |
| title | HIV-1 transmission between T cells and macrophages: consequences for viral pathogenesis. |
| title_full | HIV-1 transmission between T cells and macrophages: consequences for viral pathogenesis. |
| title_fullStr | HIV-1 transmission between T cells and macrophages: consequences for viral pathogenesis. |
| title_full_unstemmed | HIV-1 transmission between T cells and macrophages: consequences for viral pathogenesis. |
| title_short | HIV-1 transmission between T cells and macrophages: consequences for viral pathogenesis. |
| title_sort | hiv 1 transmission between t cells and macrophages consequences for viral pathogenesis |
| topic | Infectious diseases Viruses HIV/AIDS |
| work_keys_str_mv | AT baxtera hiv1transmissionbetweentcellsandmacrophagesconsequencesforviralpathogenesis |