Bristow C; International Conference on AIDS.
Int Conf AIDS. 2000 Jul 9-14; 13: abstract no. TuPpA1219.
C. Bristow, University of North Carolina Hospitals, McLendon Clinical Laboratories, 101 Manning Drive, Chapel Hill, NC 27514, United States, Tel.: +1 919 966 6100, Fax: +1 919 966 0486, E-mail: cbristow@unch.unc.edu
Resistance to HIV in U937 non-permissive cells has been shown to result from fusion/entry failure. We found that HIV permissive and non-permissive U937 promonocytic subclones differ in the subcellular location, but not the gene expression, of an HIV entry co-factor. Human leukocyte elastase (HLE), a diverse protein also known to play a role in chemotaxis and to regulate granulopoiesis, is localized only on the cell surface of the HIV permissive subclone and is only granule-associated in the non-permissive subclone. HLE subcellular localization is determined by stage of differentiation rather than mRNA sequence or processing. Translocation of granule-associated HLE to the cell surface of non-permissive cells in response to bacterial lipopolysaccharide (LPS) confers HIV permissivity. The physiologic HLE ligand, a1proteinase inhibitor (a1antitrypsin, a1PI), also known to be a chemoattractant, is shown to induce clustering and co-capping of HLE with chemokine receptors. Clustering is completely inhibited by prior exposure to chemokine. Neither permissive nor LPS-stimulated non-permissive cells produce HIV in the absence of a1PI. Peak RT activity was found to increase in direct relation to the culture concentration of a1PI. Time to peak RT activity was diminished by two days for each logarithmic dilution of virus. That time to peak RT activity was not increased by a1PI suggests that the influence of a1PI on peak RT levels was not related to viral inoculum nor time of infection. Rather, these results suggest that increased peak RT levels resulted either from an increased number of virions produced by each cell or from an increased number of infected cells. Evidence supports the participation of cell surface HLE and cell-free a1PI as HIV entry co-factors.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Chemokines
- HIV
- HIV Envelope Protein gp41
- HIV Infections
- HIV Long Terminal Repeat
- HIV Seronegativity
- HIV Seropositivity
- Humans
- Leukocyte Elastase
- Receptors, Chemokine
- Receptors, HIV
- alpha 1-Antitrypsin
- genetics
- immunology
Other ID:
UI: 102238827
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