Constitutive cell surface association between CD4 and CCR5.
HIV-1 entry into cells involves formation of a complex between gp120 of the viral envelope glycoprotein (Env), a receptor (CD4), and a coreceptor. For most strains of HIV, this coreceptor is CCR5. Here, we provide evidence that CD4 is specifically associated with CCR5 in the absence of gp120 or any...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1999
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| _version_ | 1826285756281257984 |
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| author | Xiao, X Wu, L Stantchev, T Feng, Y Ugolini, S Chen, H Shen, Z Riley, J Broder, C Sattentau, Q Dimitrov, D |
| author_facet | Xiao, X Wu, L Stantchev, T Feng, Y Ugolini, S Chen, H Shen, Z Riley, J Broder, C Sattentau, Q Dimitrov, D |
| author_sort | Xiao, X |
| collection | OXFORD |
| description | HIV-1 entry into cells involves formation of a complex between gp120 of the viral envelope glycoprotein (Env), a receptor (CD4), and a coreceptor. For most strains of HIV, this coreceptor is CCR5. Here, we provide evidence that CD4 is specifically associated with CCR5 in the absence of gp120 or any other receptor-specific ligand. The amount of CD4 coimmunoprecipitated with CCR5 was significantly higher than that with the other major HIV coreceptor, CXCR4, and in contrast to CXCR4 the CD4-CCR5 coimmunoprecipitation was not significantly increased by gp120. The CD4-CCR5 interaction probably takes place via the second extracellular loop of CCR5 and the first two domains of CD4. It can be inhibited by CCR5- and CD4-specific antibodies that interfere with HIV-1 infection, indicating a possible role in virus entry. These findings suggest a possible pathway of HIV-1 evolution and development of immunopathogenicity, a potential new target for antiretroviral drugs and a tool for development of vaccines based on Env-CD4-CCR5 complexes. The constitutive association of a seven-transmembrane-domain G protein-coupled receptor with another receptor also indicates new possibilities for cross-talk between cell surface receptors. |
| first_indexed | 2024-03-07T01:33:36Z |
| format | Journal article |
| id | oxford-uuid:946427fc-fe8b-47fa-b31c-53de12970859 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:33:36Z |
| publishDate | 1999 |
| record_format | dspace |
| spelling | oxford-uuid:946427fc-fe8b-47fa-b31c-53de129708592022-03-26T23:39:13ZConstitutive cell surface association between CD4 and CCR5.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:946427fc-fe8b-47fa-b31c-53de12970859EnglishSymplectic Elements at Oxford1999Xiao, XWu, LStantchev, TFeng, YUgolini, SChen, HShen, ZRiley, JBroder, CSattentau, QDimitrov, DHIV-1 entry into cells involves formation of a complex between gp120 of the viral envelope glycoprotein (Env), a receptor (CD4), and a coreceptor. For most strains of HIV, this coreceptor is CCR5. Here, we provide evidence that CD4 is specifically associated with CCR5 in the absence of gp120 or any other receptor-specific ligand. The amount of CD4 coimmunoprecipitated with CCR5 was significantly higher than that with the other major HIV coreceptor, CXCR4, and in contrast to CXCR4 the CD4-CCR5 coimmunoprecipitation was not significantly increased by gp120. The CD4-CCR5 interaction probably takes place via the second extracellular loop of CCR5 and the first two domains of CD4. It can be inhibited by CCR5- and CD4-specific antibodies that interfere with HIV-1 infection, indicating a possible role in virus entry. These findings suggest a possible pathway of HIV-1 evolution and development of immunopathogenicity, a potential new target for antiretroviral drugs and a tool for development of vaccines based on Env-CD4-CCR5 complexes. The constitutive association of a seven-transmembrane-domain G protein-coupled receptor with another receptor also indicates new possibilities for cross-talk between cell surface receptors. |
| spellingShingle | Xiao, X Wu, L Stantchev, T Feng, Y Ugolini, S Chen, H Shen, Z Riley, J Broder, C Sattentau, Q Dimitrov, D Constitutive cell surface association between CD4 and CCR5. |
| title | Constitutive cell surface association between CD4 and CCR5. |
| title_full | Constitutive cell surface association between CD4 and CCR5. |
| title_fullStr | Constitutive cell surface association between CD4 and CCR5. |
| title_full_unstemmed | Constitutive cell surface association between CD4 and CCR5. |
| title_short | Constitutive cell surface association between CD4 and CCR5. |
| title_sort | constitutive cell surface association between cd4 and ccr5 |
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