HIV-1 infects macrophages by exploiting an endocytic route dependent on dynamin, Rac1 and Pak1.
Recent studies provide compelling evidence that HIV-1 entry in cell lines and lymphocytes proceeds by endocytosis, but these studies are still lacking in macrophages, an important natural target cell for HIV-1. Macrophages exhibit continual and extensive endocytic activity as part of their natural f...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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2011
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| _version_ | 1826303007443124224 |
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| author | Carter, G Bernstone, L Baskaran, D James, W |
| author_facet | Carter, G Bernstone, L Baskaran, D James, W |
| author_sort | Carter, G |
| collection | OXFORD |
| description | Recent studies provide compelling evidence that HIV-1 entry in cell lines and lymphocytes proceeds by endocytosis, but these studies are still lacking in macrophages, an important natural target cell for HIV-1. Macrophages exhibit continual and extensive endocytic activity as part of their natural functions, so we investigated the uptake pathways involved in productive HIV-1 entry. We find that caveolae are not utilised by HIV-1, because the main structural proteins, caveolin-1 and 2 are absent from most human leukocytes. We then focused on macropinocytosis; we find that HIV-1 entry into macrophages is sensitive to inhibitors of Na(+)/H(+) exchange, actin rearrangement, dynamin, Rho family GTPases, and Pak1, but not to inhibitors of PI-3 kinase and myosin II. This leads us to conclude that HIV entry into macrophages proceeds by an endocytic pathway that is not classical macropinocytosis. Because of the limitations of a purely pharmacological study such as this, the final elucidation of this pathway awaits the development of reliable forward genetic approaches in authentic macrophages. |
| first_indexed | 2024-03-07T05:56:05Z |
| format | Journal article |
| id | oxford-uuid:ea8afdc8-c47a-4120-846e-e2643e4c1b48 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:56:05Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:ea8afdc8-c47a-4120-846e-e2643e4c1b482022-03-27T11:03:07ZHIV-1 infects macrophages by exploiting an endocytic route dependent on dynamin, Rac1 and Pak1.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ea8afdc8-c47a-4120-846e-e2643e4c1b48EnglishSymplectic Elements at Oxford2011Carter, GBernstone, LBaskaran, DJames, WRecent studies provide compelling evidence that HIV-1 entry in cell lines and lymphocytes proceeds by endocytosis, but these studies are still lacking in macrophages, an important natural target cell for HIV-1. Macrophages exhibit continual and extensive endocytic activity as part of their natural functions, so we investigated the uptake pathways involved in productive HIV-1 entry. We find that caveolae are not utilised by HIV-1, because the main structural proteins, caveolin-1 and 2 are absent from most human leukocytes. We then focused on macropinocytosis; we find that HIV-1 entry into macrophages is sensitive to inhibitors of Na(+)/H(+) exchange, actin rearrangement, dynamin, Rho family GTPases, and Pak1, but not to inhibitors of PI-3 kinase and myosin II. This leads us to conclude that HIV entry into macrophages proceeds by an endocytic pathway that is not classical macropinocytosis. Because of the limitations of a purely pharmacological study such as this, the final elucidation of this pathway awaits the development of reliable forward genetic approaches in authentic macrophages. |
| spellingShingle | Carter, G Bernstone, L Baskaran, D James, W HIV-1 infects macrophages by exploiting an endocytic route dependent on dynamin, Rac1 and Pak1. |
| title | HIV-1 infects macrophages by exploiting an endocytic route dependent on dynamin, Rac1 and Pak1. |
| title_full | HIV-1 infects macrophages by exploiting an endocytic route dependent on dynamin, Rac1 and Pak1. |
| title_fullStr | HIV-1 infects macrophages by exploiting an endocytic route dependent on dynamin, Rac1 and Pak1. |
| title_full_unstemmed | HIV-1 infects macrophages by exploiting an endocytic route dependent on dynamin, Rac1 and Pak1. |
| title_short | HIV-1 infects macrophages by exploiting an endocytic route dependent on dynamin, Rac1 and Pak1. |
| title_sort | hiv 1 infects macrophages by exploiting an endocytic route dependent on dynamin rac1 and pak1 |
| work_keys_str_mv | AT carterg hiv1infectsmacrophagesbyexploitinganendocyticroutedependentondynaminrac1andpak1 AT bernstonel hiv1infectsmacrophagesbyexploitinganendocyticroutedependentondynaminrac1andpak1 AT baskarand hiv1infectsmacrophagesbyexploitinganendocyticroutedependentondynaminrac1andpak1 AT jamesw hiv1infectsmacrophagesbyexploitinganendocyticroutedependentondynaminrac1andpak1 |