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| Author(s): |
Taís Aparecida Matozo de Souza
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2019-01-31 |
| Examining board members: |
Bruna Cunha de Alencar Bargieri;
Juliana Terzi Maricato;
Enrique Mario Boccardo Pierulivo;
Paula Ordonhez Rigato
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| Advisor: | Bruna Cunha de Alencar Bargieri |
| Abstract | |
Infection by human immunodeficiency virus (HIV) leads to severe immunodeficiency caused by depletion of T helper cells, the main targets of the virus. Besides T CD4+ cells, HIV-1 can infect and interact with other immune cells, including dendritic cells and macrophages. Dendritic cells are resistant to HIV infection, however, they can bind and internalize HIV in compartments and then transfer the virus to CD4+ T cells in a process called trans-infection. To promote infection, HIV-1 subverts actin cytoskeleton of host cell at several points of its cycle. In DCs, cytoskeleton is also essential to HIV-1 internalization and compartment assembly. Myosins are motor proteins that can interact with actin and take part in several cellular processes, including migration, molecular trafficking, endocytosis and lipid raft recycling. Even though there are about 40 myosin types, only myosin 2a has been investigated in trans-infection. Thus, our aim was to evaluate the role of myosins 1c and 1e in monocyte derived dendritic cell (MDDC) activation and HIV-1 internalization. We have validated the expression of 10 myosins in MDDCs by real-time PCR, and observed a down regulation of myosin 1c gene in HIV+ patients. We have evaluated cell activation in response to lipopolysaccharide (LPS) through CD86 and HLA-DR expression in myosin 1c and 1e knocked down MDDCs. There was no change in expression of activation markers in myosin 1e knocked down MDDCs compared with control cells. However, in most donors, myosin 1c knock down impaired the increase of activation markers following LPS treatment, suggesting that myosin 1c may play a role in cell activation by LPS. In addition, subcellular location of HIV-1 in MDDCs knocked down for myosin 1c and activated with LPS, was similar to immature cell phenotype. Nevertheless, we have not observed changes in the amount of HIV-1 internalized by myosin 1c or 1e knocked down MDDCs or in MDDCs treated with myosin I inhibitor. These data suggest that myosin 1c may play a role in MDDC activation and therefore alter the mechanism of HIV-1 internalization by MDDCs. (AU) | |
| FAPESP's process: | 16/11679-2 - Involvement of myosins in Dendritic cell-mediated trans-infection of HIV-1 |
| Grantee: | Taís Aparecida Matozo de Souza |
| Support Opportunities: | Scholarships in Brazil - Master |