Inhibition of HIV-1 replication by insulin, albeit at supraphysiological concentrations (10$ sp{-7}$ M) has previously been shown. The fact that this effect could only be seen at such high concentrations indicated that insulin might be acting via the IGF-1 receptor, which it may bind at highly elevated concentrations, but with much less affinity. We now show that IGF-1 can effectively inhibit HIV-1 replication in chronically infected U937 cells at concentrations similar to normal physiological concentrations. We have demonstrated that this inhibitory effect may be abrogated by the presence of anti-alpha-IR3 and anti-IGF-1 antibodies, directed towards the IGF-1 receptor and the IGF-1 protein, respectively. With the use of HIV-LTR-CAT and pSV-tat plasmids in a COS-7 system, we demonstrate that the inhibitory effect of IGF-1 occurs at the level of transcription. Finally we also show in a human U38 target cell line stably transfected with HIV-LTR-CAT, that IGF-1 maintains its inhibitory effect, although to a lesser degree than that in the COS-7 system. Lastly, it is shown that TNF-$ alpha$ acts to augment transcription of the HIV-LTR and is able to over-shadow the inhibitory effects of IGF-1 on transcription. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.27505 |
| Date | January 1997 |
| Creators | Chandok, Ravi. |
| Contributors | Wainberg, Mark A. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Microbiology and Immunology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001601591, proquestno: MQ37103, Theses scanned by UMI/ProQuest. |
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