@article{fdi:010075232,
  title = {{CD}4 receptor diversity in chimpanzees protects against {SIV} infection},
  author = {{B}ibollet-{R}uche, {F}. and {R}ussell, {R}. {M}. and {L}iu, {W}. {M}. and {S}tewart-{J}ones, {G}. {B}. {E}. and {S}herrill-{M}ix, {S}. and {L}i, {Y}. {Y}. and {L}earn, {G}. {H}. and {S}mith, {A}. {G}. and {G}ondim, {M}. {V}. {P}. and {P}lenderleith, {L}. {J}. and {D}ecker, {J}. {M}. and {E}aslick, {J}. {L}. and {W}etzel, {K}. {S}. and {C}ollman, {R}. {G}. and {D}ingh, {S}. {L}. and {F}inzih, {A}. and {A}youba, {A}hidjo and {P}eeters, {M}artine and {L}eendertz, {F}. {H}. and van {S}chijndel, {J}. and {G}oedmakers, {A}. and {T}on, {E}. and {B}oesch, {C}. and {K}uehl, {H}. and {A}randjelovic, {M}. and {D}ieguez, {P}. and {M}urai, {M}. and {C}olin, {C}. and {K}oops, {K}. and {S}peede, {S}. and {G}onder, {M}. {K}. and {M}uller, {M}. {N}. and {S}anz, {C}. {M}. and {M}organ, {D}. {B}. and {A}tencia, {R}. and {C}ox, {D}. and {P}iel, {A}. {K}. and {S}tewart, {F}. {A}. and {N}django, {J}. {B}. {N}. and {M}jungu, {D}. and {L}onsdorf, {E}. {V}. and {P}usey, {A}. {E}. and {K}wong, {P}. {D}. and {S}harp, {P}. {M}. and {S}haw, {G}. {M}. and {H}ahn, {B}. {H}.},
  editor = {},
  language = {{ENG}},
  abstract = {{H}uman and simian immunodeficiency viruses ({HIV}/{SIV}s) use {CD}4 as the primary receptor to enter target cells. {H}ere, we show that the chimpanzee {CD}4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with {SIV} envelope ({E}nv)-{CD}4 interactions. {T}esting the replication fitness of {SIV}cpz strains in {CD}4(+) {T} cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts. {T}hese differences were recapitulated in {CD}4 transfection assays, which revealed a strong association between {CD}4 genotypes and {SIV}cpz infection phenotypes. {T}he most striking differences were observed for three substitutions ({Q}25{R}, {Q}40{R}, and {P}68{T}), with {P}68{T} generating a second {N}-linked glycosylation site ({N}66) in addition to an invariant {N}32 encoded by all chimpanzee {CD}4 alleles. {I}n silico modeling and site-directed mutagenesis identified charged residues at the {CD}4-{E}nv interface and clashes between {CD}4-and {E}nv-encoded glycans as mechanisms of inhibition. {CD}4 polymorphisms also reduced {E}nv-mediated cell entry of monkey {SIV}s, which was dependent on at least one {D}1 domain glycan. {CD}4 allele frequencies varied among wild chimpanzees, with high diversity in all but the western subspecies, which appeared to have undergone a selective sweep. {O}ne allele was associated with lower {SIV}cpz prevalence rates in the wild. {T}hese results indicate that substitutions in the {D}1 domain of the chimpanzee {CD}4 can prevent {SIV} cell entry. {A}lthough some {SIV}cpz strains have adapted to utilize these variants, {CD}4 diversity is maintained, protecting chimpanzees against infection with {SIV}cpz and other {SIV}s to which they are exposed.},
  keywords = {{CD}4 ; {SIV} ; chimpanzee ; envelope glycoprotein ; glycan restriction ; {AFRIQUE} {SUBSAHARIENNE}},
  booktitle = {},
  journal = {{P}roceedings of the {N}ational {A}cademy of {S}ciences of the {U}nited {S}tates of {A}merica},
  volume = {116},
  numero = {8},
  pages = {3229--3238},
  ISSN = {0027-8424},
  year = {2019},
  DOI = {10.1073/pnas.1821197116},
  URL = {https://www.documentation.ird.fr/hor/fdi:010075232},
}