In: Retrovirology, 12 (2015), Nr. 37. pp. 1-15. ISSN 1742-4690

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PDF, English Download (3MB) | Lizenz: HIV-1 immune activation induces Siglec-1 expression and enhances viral trans-infection in blood and tissue myeloid cells by Pino, Maria ; Erkizia, Itziar ; Benet, Susana ; Erikson, Elina ; Fernández-Figueras, Maria Teresa ; Guerrero, Dolores ; Dalmau, Judith ; Ouchi, Dan ; Rausell, Antonio ; Ciuffi, Angela ; Keppler, Oliver T. ; Telenti, Amalio ; Kräusslich, Hans-Georg ; Martinez-Picado, Javier ; Izquierdo-Useros, Nuria underlies the terms of Creative Commons Attribution 3.0 Germany

Abstract

Background: Myeloid cells are key players in the recognition and response of the host against invading viruses. Paradoxically, upon HIV-1 infection, myeloid cells might also promote viral pathogenesis through trans-infection, a mechanism that promotes HIV-1 transmission to target cells via viral capture and storage. The receptor Siglec-1 (CD169) potently enhances HIV-1 trans-infection and is regulated by immune activating signals present throughout the course of HIV-1 infection, such as interferon α (IFNα). Results: Here we show that IFNα-activated dendritic cells, monocytes and macrophages have an enhanced ability to capture and trans-infect HIV-1 via Siglec-1 recognition of viral membrane gangliosides. Monocytes from untreated HIV-1-infected individuals trans-infect HIV-1 via Siglec-1, but this capacity diminishes after effective antiretroviral treatment. Furthermore, Siglec-1 is expressed on myeloid cells residing in lymphoid tissues, where it can mediate viral trans-infection. Conclusions: Siglec-1 on myeloid cells could fuel novel CD4+ T-cell infections and contribute to HIV-1 dissemination in vivo.