Initial HIV mucosal infection and dendritic cells
Autor: | Anthony L, Cunningham, Andrew N, Harman, Andrew, Harman, Najla, Nasr |
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Rok vydání: | 2013 |
Předmět: |
Pathology
medicine.medical_specialty Myeloid Receptors CCR5 Human immunodeficiency virus (HIV) mucosal transmission Biology medicine.disease_cause Intestinal epithelium Mucosal Infection medicine.anatomical_structure Intestinal mucosa Immunology HIV-1 medicine Humans Molecular Medicine Secondary lymphoid tissue dendritic cells Bone marrow Intestinal Mucosa Receptor Research Articles |
Zdroj: | EMBO Molecular Medicine |
ISSN: | 1757-4684 1757-4676 |
Popis: | The gastrointestinal tract is a principal route of entry and site of persistence of human immunodeficiency virus type 1 (HIV-1). The intestinal mucosa, being rich of cells that are the main target of the virus, represents a primary site of viral replication and CD4+ T-cell depletion. Here, we show both in vitro and ex vivo that HIV-1 of R5 but not X4 phenotype is capable of selectively triggering dendritic cells (DCs) to migrate within 30 min between intestinal epithelial cells to sample virions and transfer infection to target cells. The engagement of the chemokine receptor 5 on DCs and the viral envelope, regardless of the genetic subtype, drive DC migration. Viruses penetrating through transient opening of the tight junctions likely create a paracellular gradient to attract DCs. The formation of junctions with epithelial cells may initiate a haptotactic process of DCs and at the same time favour cell-to-cell viral transmission. Our findings indicate that HIV-1 translocation across the intestinal mucosa occurs through the selective engagement of DCs by R5 viruses, and may guide the design of new prevention strategies. |
Databáze: | OpenAIRE |
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