Verotoxin produced by Enterohemorrhagic E. coli is comprised of a catalytic A subunit and a receptor Gb3 binding B subunit pentamer. VT causes protein synthesis inhibition by ribosomal inactivation in Gb3 positive cells via receptor mediated endocytosis and retrograde transport to the ER. We propose that verotoxin is a novel inhibitor for HIV-1 infection. Experiments conducted using VT treated Jurkat-C T cells and PHA/IL-2 activated human PBMCs reveal the anti-HIV-1 property of VT is receptor Gb3 independent since the catalytic A subunit alone is sufficient for inhibition. Possible mechanism of action involves mild inhibition of protein synthesis and cell proliferation. Recent findings in our lab suggest Gb3 is a natural resistance factor for HIV-1 infection, which was further investigated by selecting a Gb3 low subpopulation in THP-1 cells using VT treatment. Selected THP-1 cells were completely resistant to HIV-1 infection, however decreased surface CXCR4 expression may be a cause.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/31440 |
| Date | 20 December 2011 |
| Creators | Shi, Peilin |
| Contributors | Lingwood, Clifford A. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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