Vpx enhances innate immune responses independently of SAMHD1 during HIV-1 infection

• DOI: 10.1186/s12977-021-00548-2
• Publication Date: 2021-02-09T11:10:35Z
• Authors: Oya Cingöz; Nicolas D. Arnow; Mireia Puig Torrents; Norbert Bannert
• Keywords: Macrophage; THP-1 Cells; 610; MDM; HIV Infections; Virus Replication; Cell Line; ISG; SAM Domain and HD Domain-Containing Protein 1; 03 medical and health sciences; ISRE; Humans; Viral Regulatory and Accessory Proteins; ddc:610; Innate immunity; ddc:610; 0303 health sciences; Research; Immunity, Innate/genetics [MeSH] ; Interferon ; Cell Line [MeSH] ; SAM Domain and HD Domain-Containing Protein 1/metabolism [MeSH] ; THP-1 Cells [MeSH] ; Virus Replication [MeSH] ; Host-Pathogen Interactions/immunology [MeSH] ; HIV-2/genetics [MeSH] ; Innate immunity ; HIV-2/physiology [MeSH] ; ISRE ; ISG ; Viral Regulatory and Accessory Proteins/genetics [MeSH] ; HIV Infections/immunology [MeSH] ; Humans [MeSH] ; HIV Infections/genetics [MeSH] ; Macrophage ; Infection ; SAM Domain and HD Domain-Containing Protein 1/immunology [MeSH] ; THP-1 ; Leukocytes, Mononuclear/virology [MeSH] ; SAM Domain and HD Domain-Containing Protein 1/genetics [MeSH] ; Proteolysis [MeSH] ; Host-Pathogen Interactions/genetics [MeSH] ; Viral Regulatory and Accessory Proteins/immunology [MeSH] ; Research ; HEK293 Cells [MeSH] ; MDM; RC581-607; Immunity, Innate; 3. Good health; HEK293 Cells; HIV-2; Host-Pathogen Interactions; Proteolysis; Leukocytes, Mononuclear; Interferon; THP-1; Immunologic diseases. Allergy; 610 Medizin und Gesundheit; Infection

Abstract Background The genomes of HIV-2 and some SIV strains contain the accessory gene vpx, which carries out several functions during infection, including the downregulation of SAMHD1. Vpx is also commonly used in experiments to increase HIV-1 infection efficiency in myeloid cells, particularly in studies that investigate the activation of antiviral pathways. However, the potential effects of Vpx on cellular innate immune signaling is not completely understood. We investigated whether and how Vpx affects ISG responses in monocytic cell lines and MDMs during HIV-1 infection.

Results HIV-1 infection at excessively high virus doses can induce ISG activation, although at the expense of high levels of cell death. At equal infection levels, the ISG response is potentiated by the presence of Vpx and requires the initiation of reverse transcription. The interaction of Vpx with the DCAF1 adaptor protein is important for the enhanced response, implicating Vpx-mediated degradation of a host factor. Cells lacking SAMHD1 show similarly augmented responses, suggesting an effect that is independent of SAMHD1 degradation. Overcoming SAMHD1 restriction in MDMs to reach equal infection levels with viruses containing and lacking Vpx reveals a novel function of Vpx in elevating innate immune responses.

Conclusions Vpx likely has as yet undefined roles in infected cells. Our results demonstrate that Vpx enhances ISG responses in myeloid cell lines and primary cells independently of its ability to degrade SAMHD1. These findings have implications for innate immunity studies in myeloid cells that use Vpx delivery with HIV-1 infection.