@article{fdi:010072863, title = {{L}oss of {CXCR}6 coreceptor usage characterizes pathogenic lentiviruses}, author = {{W}etzel, {K}. {S}. and {Y}i, {Y}. {J}. and {Y}adav, {A}. and {B}auer, {A}. {M}. and {B}ello, {E}. {A}. and {R}omero, {D}. {C}. and {B}ibollet-{R}uche, {F}. and {H}ahn, {B}. {H}. and {P}aiardini, {M}. and {S}ilvestri, {G}. and {P}eeters, {M}artine and {C}ollman, {R}. {G}.}, editor = {}, language = {{ENG}}, abstract = {{P}andemic {HIV}-1 originated from the cross-species transmission of {SIV}cpz, which infects chimpanzees, while {SIV}cpz itself emerged following the cross-species transmission and recombination of monkey {SIV}s, with env contributed by the {SIV}gsn/mus/mon lineage that infects greater spot-nosed, mustached and mona monkeys. {SIV}cpz and {HIV}-1 are pathogenic in their respective hosts, while the phenotype of their {SIV}gsn/mus/mon ancestors is unknown. {H}owever, two well-studied {SIV} infected natural hosts, sooty mangabeys ({SM}s) and {A}frican green monkeys ({AGM}s), typically remain healthy despite high viral loads; these species express low levels of the canonical coreceptor {CCR}5, and recent work shows that {CXCR}6 is a major coreceptor for {SIV} in these hosts. {I}t is not known what coreceptors were used by the precursors of {SIV}cpz, whether coreceptor use changed during emergence of the {SIV}cpz/{HIV}-1 lineage, and what {T} cell subsets express {CXCR}6 in natural hosts. {U}sing species-matched coreceptors and {CD}4, we show here that {SIV}cpz uses only {CCR}5 for entry and, like {HIV}-1, cannot use {CXCR}6. {I}n contrast, {SIV}mus efficiently uses both {CXCR}6 and {CCR}5. {C}oreceptor selectivity was determined by {E}nv, with {CXCR}6 use abrogated by {P}ro326 in the {V}3 crown, which is absent in monkey {SIV}s but highly conserved in {SIV}cpz/{HIV}-1. {T}o characterize which cells express {CXCR}6, we generated a novel antibody that recognizes {CXCR}6 of multiple primate species. {T}esting lymphocytes from {SM}, the best-studied natural host, we found that {CXCR}6 is restricted to {CD}4+ effector memory cells, and is expressed by a sub-population distinct from those expressing {CCR}5. {T}hus, efficient {CXCR}6 use, previously identified in {SM} and {AGM} infection, also characterizes a member of the {SIV} lineage that gave rise to {SIV}cpz/{HIV}-1. {L}oss of {CXCR}6 usage by {SIV}cpz may have altered its cell tropism, shifting virus from {CXCR}6-expressing cells that may support replication without disrupting immune function or homeostasis, towards {CCR}5-expressing cells with pathogenic consequences.}, keywords = {}, booktitle = {}, journal = {{PL}o{S} {P}athogens}, volume = {14}, numero = {4}, pages = {e1007003 [26 p.]}, ISSN = {1553-7366}, year = {2018}, DOI = {10.1371/journal.ppat.1007003}, URL = {https://www.documentation.ird.fr/hor/fdi:010072863}, }