@article{fdi:010073984,
  title = {{SIV}col {N}ef counteracts {SERINC}5 by promoting its proteasomal degradation but does not efficiently enhance {HIV}-1 replication in human {CD}4+{T} cells and lymphoid tissue},
  author = {{K}miec, {D}. and {A}kbil, {B}. and {A}nanth, {S}. and {H}otter, {D}. and {S}parrer, {K}. {M}. {J}. and {S}turzel, {C}. {M}. and {T}rautz, {B}. and {A}youba, {A}hidjo and {P}eeters, {M}artine and {Y}ao, {Z}. and {S}tagljar, {I}. and {P}assos, {V}. and {Z}illinger, {T}. and {G}offinet, {C}. and {S}auter, {D}. and {F}ackler, {O}. {T}. and {K}irchhoff, {F}.},
  editor = {},
  language = {{ENG}},
  abstract = {{SERINC}5 is a host restriction factor that impairs infectivity of {HIV}-1 and other primate lentiviruses and is counteracted by the viral accessory protein {N}ef. {H}owever, the importance of {SERINC}5 antagonism for viral replication and cytopathicity remained unclear. {H}ere, we show that the {N}ef protein of the highly divergent {SIV}col lineage infecting mantled guerezas ({C}olobus guereza) is a potent antagonist of {SERINC}5, although it lacks the {CD}4, {CD}3 and {CD}28 downmodulation activities exerted by other primate lentiviral {N}efs. {I}n addition, {SIV}col {N}efs decrease {CXCR}4 cell surface expression, suppress {TCR}-induced actin remodeling, and counteract {C}olobus but not human tetherin. {U}nlike {HIV}-1 {N}ef proteins, {SIV}col{N}ef induces efficient proteasomal degradation of {SERINC}5 and counteracts orthologs from highly divergent vertebrate species, such as {X}enopus frogs and zebrafish. {A} single {Y}86{F} mutation disrupts {SERINC}5 and tetherin antagonism but not {CXCR}4 down-modulation by {SIV}col {N}ef, while mutation of a {C}-proximal di-leucine motif has the opposite effect. {U}nexpectedly, the {Y}86{F} change in {SIV}col {N}ef had little if any effect on viral replication and {CD}4+ {T} cell depletion in preactivated human {CD}4+ {T} cells and in ex vivo infected lymphoid tissue. {H}owever, {SIV}col {N}ef increased virion infectivity up to 10-fold and moderately increased viral replication in resting peripheral blood mononuclear cells ({PBMC}s) that were first infected with {HIV}-1 and activated three or six days later. {I}n conclusion, {SIV}col {N}ef lacks several activities that are conserved in other primate lentiviruses and utilizes a distinct proteasome-dependent mechanism to counteract {SERINC}5. {O}ur finding that evolutionarily distinct {SIV}col {N}efs show potent anti-{SERINC}5 activity supports a relevant role of {SERINC}5 antagonism for viral fitness in vivo. {O}ur results further suggest this {N}ef function is particularly important for virion infectivity under conditions of limited {CD}4+ {T} cell activation.},
  keywords = {},
  booktitle = {},
  journal = {{PL}o{S} {P}athogens},
  volume = {14},
  numero = {8},
  pages = {e1007269 [31 p.]},
  ISSN = {1553-7366},
  year = {2018},
  DOI = {10.1371/journal.ppat.1007269},
  URL = {https://www.documentation.ird.fr/hor/fdi:010073984},
}