Deiva K, Khiati A, Hery C, Salim H, Leclerc P, Horellou P, Tardieu M. the importance of the cell-cell contact-mediated HIV connection with astrocytes and provide direct evidence to support the notion that astrocytes are HIV latent reservoirs in the central nervous system. and (23C25), even though illness has primarily been characterized as one that KN-93 is consistent with a restricted form, we.e., manifestation of early multiply spliced HIV-1 gene products such as Nef (26, 27), but no late structural gene products (18, 28). Restrictions in astrocytes are believed to take place at multiple levels, including access (29, 30), transcription (31, 32), and post-transcription (22, 33C35). A recent study demonstrates up to 20% of perivascular astrocytes can be infected by HIV and that the percentage of HIV-infected astrocytes correlates with the severity of encephalitis and dementia (36), further confirming the important tasks of HIV illness of astrocytes in HIV/neuroAIDS. The underlying mechanisms likely involve (1) HIV invasion into the CNS through astrocytes in the interface of blood-brain barriers (37C39); (2) Secretion of cytokines/chemokines by astrocytes to attract infiltration of monocytes/macrophages and CD4 T cells into the CNS and facilitate HIV spread among those cells and the CNS cells (18, 40C42); (3) Astrocyte activation (astrocytosis) and dysfunction (e.g., glutamate rate of metabolism) and production of neurotoxins and cytokines/chemokines by astrocytes to cause neuronal injury KN-93 (43C46). Importantly, latent HIV illness in the CNS has recently been linked to astrocyte activation, jeopardized neuronal integrity, and modified manifestation of epigenetic factors and cytokine/chemokines in the CNS (47). However, it should be pointed out that all the above-mentioned studies about HIV connection with astrocytes are derived from use of cell-free HIV. Cell-cell contact-mediated intercellular disease spread has recently been recognized as an important route of illness and transmission for a number of viruses including T cell leukemia disease type 1, human KN-93 being hepatitis C disease and HIV (48C50). Intercellular HIV transfer can occur among CD4 T lymphocytes, macrophages, dendritic cells, and renal Mouse monoclonal to CD45.4AA9 reacts with CD45, a 180-220 kDa leukocyte common antigen (LCA). CD45 antigen is expressed at high levels on all hematopoietic cells including T and B lymphocytes, monocytes, granulocytes, NK cells and dendritic cells, but is not expressed on non-hematopoietic cells. CD45 has also been reported to react weakly with mature blood erythrocytes and platelets. CD45 is a protein tyrosine phosphatase receptor that is critically important for T and B cell antigen receptor-mediated activation epithelial cells (51C54); it entails virological synapse formation (48, 55, 56) and viral factors KN-93 such as Env and Gag and sponsor factors such as CD4 and chemokine co-receptors CXCR4/CCR5 (56C58). This fresh route of HIV illness offers safety against anti-HIV neutralizing antibodies and exhibits decreased level of sensitivity to cART treatment (59, 60). Considering the compact nature of the cells in the CNS and the very long perceived notion that HIV is definitely introduced into the CNS by infiltrating HIV-infected macrophages/monocytes and CD4 T lymphocytes, we hypothesized that cell-cell contact plays important tasks in HIV illness with astrocytes in the CNS and formation of HIV reservoirs in these cells. In the present study, we required advantage of several recently developed HIV reporter viruses and determined the possibility of cell-cell contact-mediated HIV illness of astrocytes. We found that compared KN-93 to cell-free HIV illness, cell-cell contact between astrocytes and HIV-infected CD4 T lymphocytes led to robust HIV illness of astrocytes. Importantly, we shown that HIV successfully maintains an extremely low lever of ongoing HIV replication in astrocytes. Lastly, we showed that infectious progeny viruses were readily recovered from HIV latent astrocytes inside a cell-cell contact manner. MATERIALS AND METHODS Cells Human being 293T, human being T lymphoblastoid cell collection Jurkat and human being astrocytoma cell collection U373.MG were from American Tissue Tradition Collection (Manassas, VA). Human being T cell leukemia cell collection MT4.
Deiva K, Khiati A, Hery C, Salim H, Leclerc P, Horellou P, Tardieu M
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