Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Negatively charged albumins (NCAs) have been identified as potent inhibitors of HIV-1 replication in vitro. Time of addition studies suggest that succinylated and aconitylated human serum albumin (Suc-HSA and Aco-HSA) act at an early stage of the virus life cycle, and surface plasmon resonance (BIAcore) experiments have confirmed a direct interaction of NCAs with HIV-1 gp120. Resistance to Suc-HSA and Aco-HSA was analyzed by characterizing HIV-1 variants that were selected in cell culture after serial passage of the NL4-3 strain in the presence of the compounds. After 24 passages (126 days) we isolated variants that were resistant to Suc-HSA (>27-fold) and Aco-HSA (37-fold), as compared with the wild-type NL4-3 virus. The binding of the NCA-resistant HIV strains to CD4+ MT-4 cells could no longer be inhibited by either Suc- or Aco-HSA. The emergence of mutations in the envelope gp120 of the resistant virus paralleled the emergence of the resistant phenotype. The Suc-HSA-resistant strain was 100-fold cross-resistant to the G quartet-containing oligonucleotide AR177 (Zintevir, an HIV-binding inhibitor), and partially cross-resistant to dextran sulfate, but remained sensitive to the bicyclam AMD3100 and the chemokine SDF-1alpha, which block HIV replication by interaction with the chemokine receptor CXCR4. Furthermore, neither Suc-HSA nor Aco-HSA inhibited the binding of monoclonal antibodies 12G5 and 2D7 (directed to CXCR4 and CCR5, respectively) in SUPT-1 cells or THP-1 cells. These results confirm that NCAs bind primarily to gp120 and do not interact directly with the HIV chemokine receptor but block the binding of the virus particles (through gp120) with CD4+ cells.
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PMID:Resistance of the human immunodeficiency virus to the inhibitory action of negatively charged albumins on virus binding to CD4. 1058 Apr 4

HIV-1 infection in cell lines is very efficient, since the target population is clonal and highly dividing. However, infection of primary cells such as CD4 T lymphocytes and monocyte-derived macrophages is much more difficult, resulting in a very small percentage of infected cells. In order to study events occurring in productively infected primary cells, we determined that a way to isolate this population from bystander cells was needed. We engineered a novel HIV-1-based reporter virus called NL4-3-IRES-HSA that allows for the magnetic separation of cells infected with fully competent virions. This X4-using virus encodes for the heat-stable antigen (HSA/murine CD24) without the deletion of any viral genes by introducing an IRES sequence between HSA and the auxiliary gene Nef. Using commercial magnetic beads, we achieved efficient purification of HIV-1-infected cells (i.e. purity >85% and recovery >90%) from diverse primary cell types at early time points following infection. We used this system to accurately quantify p53 protein levels in both virus-infected and uninfected bystander primary CD4(+) T cells. We show that p53 up-regulation occurs exclusively in the infected population. We devised a strategy that allows for an efficient separation of HIV-1 infected cells from bystanders. We believe that this new reporter virus system will be of great help to study in depth how HIV-1 interacts with its host in a primary cells context.
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PMID:Efficient magnetic bead-based separation of HIV-1-infected cells using an improved reporter virus system reveals that p53 up-regulation occurs exclusively in the virus-expressing cell population. 1969 6