@article{fdi:010058823,
  title = {{H}uman tetherin exerts strong selection pressure on the {HIV}-1 group {N} {V}pu protein},
  author = {{S}auter, {D}. and {U}nterweger, {D}. and {V}ogl, {M}. and {U}smani, {S}. {M}. and {H}eigele, {A}. and {K}luge, {S}. {F}. and {H}ermkes, {E}. and {M}oll, {M}. and {B}arker, {E}. and {P}eeters, {M}artine and {L}earn, {G}. {H}. and {B}ibollet-{R}uche, {F}. and {F}ritz, {J}. {V}. and {F}ackler, {O}. {T}. and {H}ahn, {B}. {H}. and {K}irchhoff, {F}.},
  editor = {},
  language = {{ENG}},
  abstract = {{HIV}-1 groups {M} and {N} emerged within the last century following two independent cross-species transmissions of {SIV}cpz from chimpanzees to humans. {I}n contrast to pandemic group {M} strains, {HIV}-1 group {N} viruses are exceedingly rare, with only about a dozen infections identified, all but one in individuals from {C}ameroon. {P}oor adaptation to the human host may be responsible for this limited spread of {HIV}-1 group {N} in the human population. {H}ere, we analyzed the function of {V}pu proteins from seven group {N} strains from {C}ameroon, the place where this zoonosis originally emerged. {W}e found that these {N}-{V}pus acquired four amino acid substitutions ({E}15{A}, {V}19{A} and {IV}25/26{LL}) in their transmembrane domain ({TMD}) that allow efficient interaction with human tetherin. {H}owever, despite these adaptive changes, most {N}-{V}pus still antagonize human tetherin only poorly and fail to down-modulate {CD}4, the natural killer ({NK}) cell ligand {NTB}-{A} as well as the lipid-antigen presenting protein {CD}1d. {T}hese functional deficiencies were mapped to amino acid changes in the cytoplasmic domain that disrupt putative adaptor protein binding sites and an otherwise highly conserved beta {T}r{CP}-binding {DSG}xx{S} motif. {A}s a consequence, {N}-{V}pus exhibited aberrant intracellular localization and/or failed to recruit the ubiquitin-ligase complex to induce tetherin degradation. {T}he only exception was the {V}pu of a group {N} strain recently discovered in {F}rance, but originally acquired in {T}ogo, which contained intact cytoplasmic motifs and counteracted tetherin as effectively as the {V}pus of pandemic {HIV}-1 {M} strains. {T}hese results indicate that {HIV}-1 group {N} {V}pu is under strong host-specific selection pressure and that the acquisition of effective tetherin antagonism may lead to the emergence of viral variants with increased transmission fitness.},
  keywords = {{CAMEROUN}},
  booktitle = {},
  journal = {{P}los {P}athogens},
  volume = {8},
  numero = {12},
  pages = {e1003093},
  ISSN = {1553-7374},
  year = {2012},
  DOI = {10.1371/journal.ppat.1003093},
  URL = {https://www.documentation.ird.fr/hor/fdi:010058823},
}