@article{PAR00013488,
  title = {{C}aribbean and {L}a {R}{\'e}union chikungunya virus isolates differ in their capacity to induce proinflammatory th1 and nk cell responses and acute joint pathology},
  author = {{T}eo, {T}. {H}. and {H}er, {Z}. {S}. and {T}an, {J}. {J}. {L}. and {L}um, {F}. {M}. and {L}ee, {W}. {W}. {L}. and {C}han, {Y}. {H}. and {O}ng, {R}. {Y}. and {K}am, {Y}. {W}. and {L}eparc-{G}offart, {I}. and {G}allian, {P}. and {R}enia, {L}. and de {L}amballerie, {X}avier and {N}g, {L}. {F}. {P}.},
  editor = {},
  language = {{ENG}},
  abstract = {{C}hikungunya virus ({CHIKV}) is a mosquito-borne arthralgic alphavirus that has garnered international attention as an important emerging pathogen since 2005. {M}ore recently, it invaded the {C}aribbean islands and the {W}estern {H}emisphere. {I}ntriguingly, the current {CHIKV} outbreak in the {C}aribbean is caused by the {A}sian {CHIKV} genotype, which differs from the {L}a {R}eunion {LR}2006 {OPY}1 isolate belonging to the {I}ndian {O}cean lineage. {H}ere, we adopted a systematic and comparative approach against {LR}2006 {OPY}1 to characterize the pathogenicity of the {C}aribbean {CNR}20235 isolate and consequential host immune responses in mice. {E}x vivo infection using primary mouse tail fibroblasts revealed a weaker replication efficiency by {CNR}20235 isolate. {I}n the {CHIKV} mouse model, {CNR}20235 infection induced an enervated joint pathology characterized by moderate edema and swelling, independent of mononuclear cell infiltration. {B}ased on systemic cytokine analysis, localized immunophenotyping, and gene expression profiles in the popliteal lymph node and inflamed joints, two pathogenic phases were defined for {CHIKV} infection: early acute (2 to 3 days postinfection [dpi]) and late acute (6 to 8 dpi). {R}educed joint pathology during early acute phase of {CNR}20235 infection was associated with a weaker proinflammatory {T}h1 response and natural killer ({NK}) cell activity. {T}he pathological role of {NK} cells was further demonstrated as depletion of {NK} cells reduced joint pathology in {LR}2006 {OPY}1. {T}aken together, this study provides evidence that the {C}aribbean {CNR}20235 isolate has an enfeebled replication and induces a less pathogenic response in the mammalian host. {IMPORTANCE} {T}he introduction of {CHIKV} in the {A}mericas has heightened the risk of large-scale outbreaks due to the close proximity between the {U}nited {S}tates and the {C}aribbean. {T}he immunopathogenicity of the circulating {C}aribbean {CHIKV} isolate was explored, where it was demonstrated to exhibit reduced infectivity resulting in a weakened joint pathology. {A}nalysis of serum cytokine levels, localized immunophenotyping, and gene expression profiles in the organs revealed that a limited {T}h1 response and reduced {NK} cells activity could underlie the reduced pathology in the host. {I}nterestingly, higher asymptomatic infections were observed in the {C}aribbean compared to the {L}a {R}eunion outbreaks in 2005 and 2006. {T}his is the first study that showed an association between key proinflammatory factors and pathology-mediating leukocytes with a less severe pathological outcome in {C}aribbean {CHIKV} infection. {G}iven the limited information regarding the sequela of {C}aribbean {CHIKV} infection, our study is timely and will aid the understanding of this increasingly important disease.},
  keywords = {{REUNION} ; {CARAIBES}},
  booktitle = {},
  journal = {{J}ournal of {V}irology},
  volume = {89},
  numero = {15},
  pages = {7955--7969},
  ISSN = {0022-538{X}},
  year = {2015},
  DOI = {10.1128/jvi.00909},
  URL = {https://www.documentation.ird.fr/hor/{PAR}00013488},
}