Autor(es)Teo Teck-Hui, Her Zhisheng, Tan Jeslin J L, Lum Fok-Moon, Lee Wendy W L, Chan Yi-Hao, Ong Ruo-Yan, Kam Yiu-Wing, Leparc-Goffart Isabelle, Gallian Pierre, Rénia Laurent, de Lamballerie Xavier, Ng Lisa F P

ResumoChikungunya virus (CHIKV) is a mosquito-borne arthralgic alphavirus that has garnered international attention as an important emerging pathogen since 2005. More recently, it invaded the Caribbean isl-s - the Western Hemisphere. Intriguingly, the current CHIKV outbreak in the Caribbean is caused by the Asian CHIKV genotype, which differs from the La Réunion LR2006 OPY1 isolate belonging to the Indian Ocean lineage. Here, we adopted a systematic - comparative approach against LR2006 OPY1 to characterize the pathogenicity of the Caribbean CNR20235 isolate - consequential host immune responses in mice. Ex vivo infection using primary mouse tail fibroblasts revealed a weaker replication efficiency by CNR20235 isolate. In the CHIKV mouse model, CNR20235 infection induced an enervated joint pathology characterized by moderate edema - swelling, independent of mononuclear cell infiltration. Based on systemic cytokine analysis, localized immunophenotyping, - gene expression profiles in the popliteal lymph node - inflamed joints, two pathogenic phases were defined for CHIKV infection: early acute (2 to 3 days postinfection [dpi]) - late acute (6 to 8 dpi). Reduced joint pathology during early acute phase of CNR20235 infection was associated with a weaker proinflammatory Th1 response - natural killer (NK) cell activity. The pathological role of NK cells was further demonstrated as depletion of NK cells reduced joint pathology in LR2006 OPY1. Taken together, this study provides evidence that the Caribbean CNR20235 isolate has an enfeebled replication - induces a less pathogenic response in the mammalian host. The introduction of CHIKV in the Americas has heightened the risk of large-scale outbreaks due to the close proximity between the United States - the Caribbean. The immunopathogenicity of the circulating Caribbean CHIKV isolate was explored, where it was demonstrated to exhibit reduced infectivity resulting in a weakened joint pathology. Analysis of serum cytokine levels, localized immunophenotyping, - gene expression profiles in the organs revealed that a limited Th1 response - reduced NK cells activity could underlie the reduced pathology in the host. Interestingly, higher asymptomatic infections were observed in the Caribbean compared to the La Réunion outbreaks in 2005 - 2006. This is the first study that showed an association between key proinflammatory factors - pathology-mediating leukocytes with a less severe pathological outcome in Caribbean CHIKV infection. Given the limited information regarding the sequela of Caribbean CHIKV infection, our study is timely - will aid the underst-ing of this increasingly important disease.

ImprentaJournal of Virology, v. 89, n. 15, p. 7955-7969, 2015

DescritoresChikungunya virus - Biochemistry ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Immune response ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Cytokines ; Chikungunya virus - Immune response ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Epidemiology ; Chikungunya virus - Immunology ; Chikungunya virus - Public health

Data de Publicação:2015