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| Content Provider | PubMed Central |
|---|---|
| Author | Francesco, Maria A. De Baronio, Manuela Fiorentini, Simona Signorini, Costantino Bonfanti, Carlo Claudio, Poiesi Popovic, Mikulas Grassi, Manuela Garrafa, Emirena Bozzo, Luisa Lewis, George K. Stefano, Licenziati Gallo, Robert C. Caruso, Arnaldo |
| Copyright Year | 2002 |
| Abstract | Purified recombinant HIV-1 p17 matrix protein significantly increased HIV-1 replication in preactivated peripheral blood mononuclear cell cultures obtained from healthy donors. Because HIV-1 infection and replication is related to cell activation and differentiation status, in the present study, we investigated the role played by p17 during the process of T cell stimulation. Using freshly isolated peripheral blood mononuclear cells, we demonstrate that p17 was able to enhance levels of tumor necrosis factor α and IFN-γ released from cells stimulated by IL-2. IL-4 was found to down-regulate IFN-γ and tumor necrosis factor α, and p17 restored the ability of cells to produce both cytokines. The property of p17 to increase production of proinflammatory cytokines could be a mechanism exploited by the virus to create a more suitable environment for HIV-1 infection and replication. Our data show that p17 exerts its biological activity after binding to a specific cellular receptor expressed on activated T lymphocytes. The functional p17 epitope involved in receptor binding was found to be located at the NH2-terminal region of viral protein. Immunization of BALB/c mice with a 14-aa synthetic peptide representative of the HIV-1 p17 functional region (SGGELDRWEKIRLR) resulted in the development of p17 neutralizing antibodies capable of blocking the interaction between p17 and its cellular receptor. Our results define a role for p17 in HIV-1 pathogenesis and contribute to our understanding of the molecular mechanism of HIV-1 infection and the development of additional antiviral therapeutic strategies. |
| Related Links | http://dx.doi.org/10.1073/pnas.142274699 |
| Ending Page | 9977 |
| Page Count | 6 |
| Starting Page | 9972 |
| File Format | |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 15 |
| Volume Number | 99 |
| Language | English |
| Publisher | The National Academy of Sciences |
| Publisher Date | 2002-07-23 |
| Access Restriction | Open |
| Rights Holder | The National Academy of Sciences |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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