DDX3 in HIV-1 infection and sensing: A paradox

Melissa Stunnenberg; Teunis B H Geijtenbeek; Sonja I Gringhuis

doi:10.1016/j.cytogfr.2018.03.001

DDX3 in HIV-1 infection and sensing: A paradox

Cytokine Growth Factor Rev. 2018 Apr:40:32-39. doi: 10.1016/j.cytogfr.2018.03.001. Epub 2018 Mar 8.

Authors

Melissa Stunnenberg¹, Teunis B H Geijtenbeek¹, Sonja I Gringhuis²

Affiliations

¹ Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
² Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: [email protected].

PMID: 29580812
DOI: 10.1016/j.cytogfr.2018.03.001

Abstract

HIV-1 sensors and their signaling features have been an ongoing topic of intense research over the last decade, as these mechanisms fail to establish protective immunity against HIV-1. Here, we discuss how HIV-1 infects dendritic cells (DCs) and which sensors play a role in recognizing viral DNA and RNA in these specialized immune cells. We will elaborate on the RNA helicase DDX3, which is crucial in translation initiation of HIV-1 mRNA, but also fulfills an important role as RNA sensor and inducer of antiviral immunity in DCs. As DDX3 is indispensable for HIV-1 replication, the virus cannot escape sensing by DDX3, which is an important aspect of its function. Last but not least, we will discuss how HIV-1 suppresses DDX3 sensing and how this impacts the viral load in HIV-1-infected individuals.

Keywords: DC-SIGN; DDX3; Dendritic cells; HIV-1; MAVS; PLK1; RNA sensing; Type I interferon response.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Adaptor Proteins, Signal Transducing / metabolism
Cell Adhesion Molecules / metabolism
Cell Cycle Proteins / metabolism
DEAD-box RNA Helicases / immunology
DEAD-box RNA Helicases / metabolism*
DNA, Viral / immunology*
Dendritic Cells / immunology
Dendritic Cells / virology*
HIV Infections / immunology*
HIV-1 / immunology*
Host-Pathogen Interactions / immunology*
Humans
Lectins, C-Type / metabolism
Peptide Chain Initiation, Translational / physiology
Polo-Like Kinase 1
Protein Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins / metabolism
RNA, Viral / immunology*
Receptors, Cell Surface / metabolism
Viral Load
Virus Replication / physiology

Substances

Adaptor Proteins, Signal Transducing
Cell Adhesion Molecules
Cell Cycle Proteins
DC-specific ICAM-3 grabbing nonintegrin
DNA, Viral
Lectins, C-Type
MAVS protein, human
Proto-Oncogene Proteins
RNA, Viral
Receptors, Cell Surface
Protein Serine-Threonine Kinases
DDX3X protein, human
DEAD-box RNA Helicases

Grants and funding

670424/ERC_/European Research Council/International