Chikungunya disease in nonhuman primates involves long-term viral persistence in macrophages

Autor(es): Labadie, Karine; Larcher, Thibaut; Joubert, Christophe; Mannioui, Abdelkrim; Delache, Benoit; Brochard, Patricia; Guigand, Lydie; Dubreil, Laurence; Lebon, Pierre; Verrier, Bernard; de Lamballerie, Xavier; Suhrbier, Andreas; Cherel, Yan; Le Grand, Roger; Roques, Pierre


Resumo: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that induces in humans a disease characterized by fever, rash, and pain in muscles and joints. The recent emergence or reemergence of CHIKV in the Indian Ocean Islands and India has stressed the need to better understand the pathogenesis of this disease. Previous CHIKV disease models have used young or immunodeficient mice, but these do not recapitulate human disease patterns and are unsuitable for testing immune-based therapies. Herein, we describe what we believe to be a new model for CHIKV infection in adult, immunocompetent cynomolgus macaques. CHIKV infection in these animals recapitulated the viral, clinical, and pathological features observed in human disease. In the macaques, long-term CHIKV infection was observed in joints, muscles, lymphoid organs, and liver, which could explain the long-lasting CHIKV disease symptoms observed in humans. In addition, the study identified macrophages as the main cellular reservoirs during the late stages of CHIKV infection in vivo. This model of CHIKV physiopathology should allow the development of new therapeutic and/or prophylactic strategies.


Palavras-Chave: Alphavirus Infections - virology, Animals, Humans, Joints - pathology, Joints - virology, Liver - pathology, Liver - virology, Lymphoid tissue - pathology, Lymphoid tissue - virology, Macaca fascicularis, Macrophages - pathology, Macrophages - virology, Mice, Muscles - pathology, Muscles - virology


Imprenta: Journal of Clinical Investigation, v. 120, n. 3, p. 894-906, 2010.


Descritores: Zika virus - Arbovirus ; Zika virus - Cell ; Zika virus - Genome ; Zika virus - Immune response ; Zika virus - Pathogenesis ; Zika virus - DNA ; Zika virus - RNA ; Zika virus - Protein synthesis ; Zika virus - Proteins ; Zika virus - Antibodies ; Zika virus - Autoimmunity ; Zika virus - Cytokines ; Zika virus - Immunology ; Zika virus - Infectious diseases ; Zika virus - Inflammation ; Zika virus - Serology ; Zika virus - T lymphocytes ; Zika virus - Viral infections ; Zika virus - Clinical examination ; Zika virus - Molecular methods ; Zika virus - PCR detection ; Zika virus - Real Time PCR ; Zika virus - RNA virus ; Zika virus - RT-PCR ; Zika virus - Transmission ; Zika virus - Vaccine ; Zika virus - Chikungunya Fever ; Zika virus - Epidemiology ; Zika virus - Head size ; Zika virus - Public health ; Zika virus - Rash maculopapular


Data de publicação: 2010