Chikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants
Autor(es): Lee Chia Yin, Kam Yiu-Wing, Fric Jan, Malleret Benoit, Koh Esther G L, Prakash Celine, Huang Wen, Lee Wendy W L, Lin Cui, Lin Raymond T P, Renia Laurent, Wang Cheng-I, Ng Lisa F P, Warter Lucile
Resumo: Chikungunya virus (CHIKV) is an alphavirus responsible for numerous epidemics throughout Africa - Asia, causing infectious arthritis - reportedly linked with fatal infections in newborns - elderly. Previous studies in animal models indicate that humoral immunity can protect against CHIKV infection, but despite the potential efficacy of B-cell-driven intervention strategies, there are no virus-specific vaccines or therapies currently available. In addition, CHIKV has been reported to elicit long-lasting virus-specific IgM in humans, - to establish long-term persistence in non-human primates, suggesting that the virus might evade immune defenses to establish chronic infections in man. However, the mechanisms of immune evasion potentially employed by CHIKV remain uncharacterized. We previously described two human monoclonal antibodies that potently neutralize CHIKV infection. In the current report, we have characterized CHIKV mutants that escape antibody-dependent neutralization to identify the CHIKV E2 domain B - fusion loop groove" as the primary determinants of CHIKV interaction with these antibodies. Furthermore, for the first time, we have also demonstrated direct CHIKV cell-to-cell transmission, as a mechanism that involves the E2 domain A - that is associated with viral resistance to antibody-dependent neutralization. Identification of CHIKV sub-domains that are associated with human protective immunity, will pave the way for the development of CHIKV-specific sub-domain vaccination strategies. Moreover, the clear demonstration of CHIKV cell-to-cell transmission - its possible role in the establishment of CHIKV persistence, will also inform the development of future anti-viral interventions. These data shed new light on CHIKV-host interactions that will help to combat human CHIKV infection - inform future studies of CHIKV pathogenesis."
Imprenta: PLoS Pathogens, v. 7, n. 12, p. e1002390, 2011
Identificador do objeto digital: 10.1371/journal.ppat.1002390
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Molecular structure ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Transmission ; Chikungunya virus - Vaccine ; Chikungunya virus - Epidemic ; Chikungunya virus - Immunology
Data de publicação: 2011
