Exogenous HIV-1 Vpr disrupts IFN-alpha response by plasmacytoid dendritic cells (pDCs) and subsequent pDC/NK interplay.
HIV Vpr is known for its immunomodulatory capacities including its impairment of NK cell functions. However, the role of pDCs in this context remains elusive. We show that synthetic Vpr substantially inhibits type I IFN production by pDCs without inducing apoptosis in pDCs. Furthermore, we found that exogenous Vpr compromises subsequent pDC/NK interplay as shown by diminished IFN-gamma production by NK cells. Thus, Vpr-mediated dysregulation of IFN-alpha and IFN-gamma production affects key components of the innate immune response supporting an essential role of Vpr in HIV pathogenesis.
Hong
Henoch Sangjoon
HS
Clinic for Immunology und Rheumatology, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, Hannover, Germany.
Bhatnagar
Nupur
N
Ballmaier
Matthias
M
Schubert
Ulrich
U
Henklein
Peter
P
Volgmann
Thorsten
T
Heiken
Hans
H
Schmidt
Reinhold E
RE
Meyer-Olson
Dirk
D
D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D016898:Interferon-alpha / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D019899:Paracrine Communication; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology
D007155:Immunologic Factors; D016898:Interferon-alpha; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1; D007371:Interferon-gamma