HIV-1 Gag-virus-like particles inhibit HIV-1 replication in dendritic cells and T cells through IFN-α-dependent upregulation of APOBEC3G and 3F.
Human immunodeficiency virus-1 (HIV-1) infection and the acquired immune deficiency syndrome (AIDS) pandemic remain global threats in the absence of a protective or a therapeutic vaccine. HIV-1 replication is reportedly inhibited by some cellular factors, including APOBEC3G (A3G) and APOBEC3F (A3F), which are well known inhibitors of HIV-1. Recently, HIV-1 Gag-virus-like particles (Gag-VLPs) have been shown to be safe and potent HIV-1 vaccine candidates that can elicit strong cellular and humoral immunity without need of any adjuvant. In this report, we stimulated human monocyte-derived dendritic cells (DCs) with Gag-VLPs and we demonstrated that Gag-VLP-treated DCs (VLP-DCs) produced interferon alpha (IFN-α), along with an increase in mRNA and protein expression of A3G and A3F. Gag-VLPs inhibited HIV-1 replication not only in DCs themselves, but also in cocultured T cells in an IFN-α-dependent manner. In addition, A3G/3F content in HIV virions released from VLP-DCs increased. Both the increase in A3G/3F expression and the inhibition of HIV-1 replication were reversed by anti-IFN-α or anti-IFNAR antibodies. Our findings in this study provide insight into the mechanism of Gag-VLP-induced inhibition of HIV-1 replication in DCs and T cells.
Department of Life and Environmental Sciences, Chiba Institute of Technology, Chiba, Japan. c_myintoo@hotmail.com
Myint Oo
MO
Chang
Tomoyuki
T
Suzuki
Norio
N
Yamamoto
Megumi
M
Watanabe
Hiroshi
H
Takaku
D000071480:APOBEC-3G Deaminase; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D003564:Cytidine Deaminase / Q000187:drug effects / Q000378:metabolism*; D043525:Cytosine Deaminase / Q000187:drug effects / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D018411:Spodoptera; D013601:T-Lymphocytes / Q000821:virology; D015854:Up-Regulation; D014771:Virion / Q000378:metabolism / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism / Q000494:pharmacology*
D016898:Interferon-alpha; D054301:gag Gene Products, Human Immunodeficiency Virus; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase