The interferon-induced expression of APOBEC3G in human blood-brain barrier exerts a potent intrinsic immunity to block HIV-1 entry to central nervous system.
In the human genome, the APOBEC3 gene has expanded into a tandem array of genes termed APOBEC3A-H. Several members of this family have potent anti-HIV-1 activity. Here we demonstrate that APOBEC-3B/3C/3F and -3G are expressed in all major cellular components of the CNS. Moreover, we show that both interferon-alpha (IFN-alpha) and IFN-gamma significantly enhance the expression of APOBEC-3G/3F and drastically inhibit HIV-1 replication in primary human brain microvascular endothelial cells (BMVECs), the major component of blood-brain barrier (BBB). As the viral inhibition can be neutralized by APOBEC3G-specific siRNA, APOBEC3G plays a key role to mediate the anti-HIV-1 activity of IFN-alpha and/or IFN-gamma. Our findings suggest that, in addition to the restriction at viral entry level, the restriction from APOBEC3 family could account for the low-level replication of HIV-1 in BMVECs. The manipulation of IFN-APOBEC3 signaling pathway could be a potent therapeutic strategy to prevent HIV invasion to central nervous system (CNS).
Argyris
Elias G
EG
Department of Medicine, Division of Infectious Diseases, Center for Human Virology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Acheampong
Edward
E
Wang
Fengxiang
F
Huang
Jialing
J
Chen
Keyang
K
Mukhtar
Muhammad
M
Zhang
Hui
H
D000071480:APOBEC-3G Deaminase; D000998:Antiviral Agents / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002490:Central Nervous System / Q000821:virology*; D003564:Cytidine Deaminase / Q000378:metabolism / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007109:Immunity / Q000187:drug effects / Q000502:physiology*; D007372:Interferons / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
D000998:Antiviral Agents; D007372:Interferons; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase