Liposome targeting to human immunodeficiency virus type 1-infected cells via recombinant soluble CD4 and CD4 immunoadhesin (CD4-IgG)
| Autor: | Elizabeth Pretzer, Diana L. Flasher, Avi Ashkenazi, Krystyna Konopka, Steven M. Chamow, Nejat Düzgüneş, Paul Dazin |
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| Rok vydání: | 1994 |
| Předmět: |
CD4 immunoadhesin
Biophysics Biology HIV Envelope Protein gp120 Gp41 Biochemistry Flow cytometry Viral envelope medicine Humans Staphylococcal Protein A Cell Line Transformed Liposome Drug Carriers medicine.diagnostic_test Virulence virus diseases Cell Biology Flow Cytometry Molecular biology Fragment crystallizable region Ectodomain CD4 Antigens Liposomes biology.protein HIV-1 Protein A CD4 Immunoadhesins |
| Zdroj: | Biochimica et biophysica acta. 1194(1) |
| ISSN: | 0006-3002 |
| Popis: | HIV-infected cells producing virions express the viral envelope glycoprotein gp120/gp41 on their surface. We examined whether liposomes coupled to recombinant soluble CD4 (sCD4, the ectodomain of CD4 which binds gp120 with high affinity) could specifically bind to HIV-infected cells. sCD4 was chemically coupled by 2 different methods to liposomes containing rhodamine-phosphatidylethanolamine in their membrane as a fluorescent marker. In one method, sCD4 was thiolated with N- succinimidyl acetylthioacetate (SATA) and coupled to liposomes via a malcimide-derivatised phospholipid. In the other method, the oligosaccharides on sCD4 were coupled to a. sulfhydryl-derivatised phospholipid, utilizing the bifunctional reagent, 4-(4-N- maleimidophenyl ) butyric acid hydrazide (MPBH). The association of the liposomes with HIV-1-infected or uninfected cells was examined by flow cytometry. CD4-coupled liposomes associated specifically to chronically infected H9/HTLV-IIIB cells, but not to uninfected H9 cells. CD4-coupled liposomes also associated specifically with monocytic THP-1 cells chronically infected with HIV-1 (THP-1/HIV-1IIIB). Control liposomes without coupled CD4 did not associate significantly with any of the cells, while free sCD4 could competitively inhibit the association of the CD4-coupled liposomes with the infected cells. The chimeric molecule CD4-immunoadhesin (CD4-IgG) could also be used as a ligand to target liposomes with covalently coupled Protein A (which binds the Fc region of the CD4-IgG) to H9/HTLV-IIIB cells. The CD4-liposomes inhibited the infectivity of HIV-1 in A3.01 cells, and also bound rgp120. Our results suggest that liposomes containing antiviral or cytotoxic agents may be targeted specifically to HIV-infected cells. |
| Databáze: | OpenAIRE |
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