@article{fdi:010070963,
  title = {{P}rimate lentiviruses use at least three alternative strategies to suppress {NF}-kappa {B}-mediated immune activation},
  author = {{H}otter, {D}. and {K}rabbe, {T}. and {R}eith, {E}. and {G}awanbacht, {A}. and {R}ahm, {N}. and {A}youba, {A}hidjo and {V}an {D}riessche, {B}. and {V}an {L}int, {C}. and {P}eeters, {M}artine and {K}irchhoff, {F}. and {S}auter, {D}.},
  editor = {},
  language = {{ENG}},
  abstract = {{P}rimate lentiviruses have evolved sophisticated strategies to suppress the immune response of their host species. {F}or example, {HIV}-2 and most simian immunodeficiency viruses ({SIV}s) use their accessory protein {N}ef to prevent {T} cell activation and antiviral gene expression by downmodulating the {T} cell receptor {CD}3. {T}his {N}ef function was lost in {HIV}-1 and other vpu-encoding viruses suggesting that the acquisition of {V}pu-mediated {NF}-kappa {B} inhibition reduced the selection pressure for inhibition of {T} cell activation by {N}ef. {T}o obtain further insights into the modulation of {NF}-kappa {B} activity by primate lentiviral accessory factors, we analyzed 32 {V}pr proteins from a large panel of divergent primate lentiviruses. {W}e found that those of {SIV}col and {SIV}olc infecting {C}olobinae monkeys showed the highest efficacy in suppressing {NF}-kappa {B} activation. {V}pr-mediated inhibition of {NF}-kappa {B} resulted in decreased {IFN} beta promoter activity and suppressed type {I} {IFN} induction in virally infected primary cells. {I}nterestingly, {SIV}col and {SIV}olc differ from all other primate lentiviruses investigated by the lack of both, a vpu gene and efficient {N}ef-mediated downmodulation of {CD}3. {T}hus, primate lentiviruses have evolved at least three alternative strategies to inhibit {NF}-kappa {B}-dependent immune activation. {F}unctional analyses showed that the inhibitory activity of {SIV}olc and {SIV}col {V}prs is independent of {DCAF}1 and the induction of cell cycle arrest. {W}hile both {V}prs target the {IKK} kinase complex or a factor further downstream in the {NF}-kappa {B} signaling cascade, only {SIV}olc {V}pr stabilizes {I} kappa {B} alpha and inhibits p65 phosphorylation. {N}otably, only de-novo synthesized but not virion-associated {V}pr suppressed the activation of {NF}-kappa {B}, thus enabling {NF}-kappa {B}-dependent initiation of viral gene transcription during early stages of the replication cycle, while minimizing antiviral gene expression at later stages. {O}ur findings highlight the key role of {NF}-kappa {B} in antiviral immunity and demonstrate that primate lentiviruses follow distinct evolutionary paths to modulate {NF}-kappa {B}-dependent expression of viral and antiviral genes.},
  keywords = {},
  booktitle = {},
  journal = {{PLOS} {P}athogens},
  volume = {13},
  numero = {8},
  pages = {e1006598 [28 p.]},
  ISSN = {1553-7366},
  year = {2017},
  DOI = {10.1371/journal.ppat.1006598},
  URL = {https://www.documentation.ird.fr/hor/fdi:010070963},
}