Viral evasion of DNA-stimulated innate immune responses

Christensen, Maria H; Paludan, Søren R

As described above the retroviral replication intermediates, ssDNA, Y-form DNA, RNA:DNA hybrids and dsDNA are recognized by cGAS as well as by IFI16. It is thus conceivable that retroviruses have evolved different mechanisms for inhibition of the DNA sensing pathway. HIV-1 is known to target the RLR pathway via a relocalization of RIG-I to lysosomes and perinuclear compartments through a mechanism dependent on the viral protease, 78 but knowledge about inhibition of the DNA sensing pathway is still insufficient. Recently, the two HIV-1 proteins Vpr and Vif were reported to target and inactivate TBK1 in dendritic-and macrophage-like cells. 79 TBK1 was found to be ubiquitinated, as a normal response to TRAF3 activation, but the subsequent autophosphorylation of TBK1 was lacking due to Vpr and Vif expression. Vpr and Vif were found to interact with TBK1 and as both proteins are present in the incoming virus particle, it is possible that HIV-1 inhibits DNA receptor-dependent signaling at early time points post-viral entry. 79