O'nyong-nyong Virus, Chad

Bessaud, Maël; Peyrefitte, Christophe N.; Pastorino, Boris; Gravier, P.; Tock, Fabienne; Boete, Fabrice; Tolou, Hugues; Grandadam, Marc

doi:10.3201/eid1208.060199

Cited by 31 publications

(21 citation statements)

References 11 publications

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“…The WT‐CHIKV isolate (LR2006‐OPY1) used for challenge experiments was isolated from an infected patient during the Reunion Island Outbreak in 2005–2006 (Bessaud et al , ). The WT‐ONNV isolate used for cross‐protection challenge experiments was isolated from an infected patient from Chad in 2004 (Bessaud et al , ). NsP‐mutant CHIKV infectious clones were generated by recombination technology, PCR‐based site‐directed mutagenesis, and sub‐cloning from the full‐length infectious cDNA clone of the CHIKV LR2006‐OPY1 isolate, as previously described (Saul et al , ).…”

Section: Methodsmentioning

confidence: 99%

Mutating chikungunya virus non‐structural protein produces potent live‐attenuated vaccine candidate

et al. 2019

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Currently, there are no commercially available live‐attenuated vaccines against chikungunya virus ( CHIKV ). Here, CHIKV s with mutations in non‐structural proteins (nsPs) were investigated for their suitability as attenuated CHIKV vaccines. R532H mutation in nsP1 caused reduced infectivity in mouse tail fibroblasts but an enhanced type‐I IFN response compared to WT ‐ CHIKV . Adult mice infected with this nsP‐mutant exhibited a mild joint phenotype with low‐level viremia that rapidly cleared. Mechanistically, ingenuity pathway analyses revealed a tilt in the anti‐inflammatory IL ‐10 versus pro‐inflammatory IL ‐1β and IL ‐18 balance during CHIKV nsP‐mutant infection that modified acute antiviral and cell signaling canonical pathways. Challenging CHIKV nsP‐mutant‐infected mice with WT ‐ CHIKV or the closely related O'nyong‐nyong virus resulted in no detectable viremia, observable joint inflammation, or damage. Challenged mice showed high antibody titers with efficient neutralizing capacity, indicative of immunological memory. Manipulating molecular processes that govern CHIKV replication could lead to plausible vaccine candidates against alphavirus infection.

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Section: Methodsmentioning

confidence: 99%

Mutating chikungunya virus non‐structural protein produces potent live‐attenuated vaccine candidate

et al. 2019

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“…Full-length CHIKV and ONNV infectious clones were produced using standard molecular biology techniques similar to those previously described (24). Gaussia luciferase (Gluc) from Gaussia princeps was inserted into CHIKV isolates from Reunion Island (LR2006 OPY1), Singapore (SGP11) (25), the Caribbean region (CNR20235) (26), and ONNV (27), at a site between the nonstructural and structural genes, together with an extra copy of the subgenomic promoter to ensure expression of the structural proteins. Similarly, CHIKV-LR2006 OPY1 was tagged with ZsGreen from Anthozoa reef coral.…”

Section: Methodsmentioning

confidence: 99%

The Antiviral Alkaloid Berberine Reduces Chikungunya Virus-Induced Mitogen-Activated Protein Kinase Signaling

Varghese

Thaa

Amrun

et al. 2016

J Virol

121

103

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Chikungunya virus (CHIKV) has infected millions of people in the tropical and subtropical regions since its reemergence in the last decade. We recently identified the nontoxic plant alkaloid berberine as an antiviral substance against CHIKV in a highthroughput screen. Here, we show that berberine is effective in multiple cell types against a variety of CHIKV strains, also at a high multiplicity of infection, consolidating the potential of berberine as an antiviral drug. We excluded any effect of this compound on virus entry or on the activity of the viral replicase. A human phosphokinase array revealed that CHIKV infection specifically activated the major mitogen-activated protein kinase (MAPK) signaling pathways extracellular signal-related kinase (ERK), p38 and c-Jun NH 2 -terminal kinase (JNK). Upon treatment with berberine, this virus-induced MAPK activation was markedly reduced. Subsequent analyses with specific inhibitors of these kinases indicated that the ERK and JNK signaling cascades are important for the generation of progeny virions. In contrast to specific MAPK inhibitors, berberine lowered virus-induced activation of all major MAPK pathways and resulted in a stronger reduction in viral titers. Further, we assessed the in vivo efficacy of berberine in a mouse model and measured a significant reduction of CHIKV-induced inflammatory disease. In summary, we demonstrate the efficacy of berberine as a drug against CHIKV and highlight the importance of the MAPK signaling pathways in the alphavirus infectious cycle. IMPORTANCEChikungunya virus (CHIKV) is a mosquito-borne virus that causes severe and persistent muscle and joint pain and has recently spread to the Americas. No licensed drug exists to counter this virus. In this study, we report that the alkaloid berberine is antiviral against different CHIKV strains and in multiple human cell lines. We demonstrate that berberine collectively reduced the virus-induced activation of cellular mitogen-activated protein kinase signaling. The relevance of these signaling cascades in the viral life cycle was emphasized by specific inhibitors of these kinase pathways, which decreased the production of progeny virions. Berberine significantly reduced CHIKV-induced inflammatory disease in a mouse model, demonstrating efficacy of the drug in vivo. Overall, this work makes a strong case for pursuing berberine as a potential anti-CHIKV therapeutic compound and for exploring the MAPK signaling pathways as antiviral targets against alphavirus infections. C hikungunya virus (CHIKV) is the causative agent of chikungunya fever, a disease spread by Aedes mosquitoes and characterized by a sudden onset of febrile illness, nausea, headache, and most importantly, severe and persistent musculoskeletal pain (1). It reemerged in tropical Asia and Africa 1 decade ago and since 2013 has infected more than 1.5 million people in the Americas (2). So far, no licensed vaccine or antiviral treatment exists to counter this disease. Over the years, many research groups have focused on...

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“…The WT ONNV isolate (IMTSSA/5163) was isolated from a patient in Chad in 2004 (kindly provided by Marc Grandadam from Unité de Virologie Tropicale, IMTSSA, Marseille, France) (11). Virus isolation was attempted by incubation of patient peripheral blood mononuclear cells collected on day of illness onset with C6/36 (Aedes albopictus) (ATCC CRL-1660) and Vero E6 (ATCC CRL-1586) monolayers.…”

Section: Virusmentioning

confidence: 99%

Longitudinal [18F]FB-IL-2 PET Imaging to Assess the Immunopathogenicity of O'nyong-nyong Virus Infection

et al. 2020

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O'nyong-nyong Virus, Chad

Cited by 31 publications

References 11 publications

Mutating chikungunya virus non‐structural protein produces potent live‐attenuated vaccine candidate

Mutating chikungunya virus non‐structural protein produces potent live‐attenuated vaccine candidate

The Antiviral Alkaloid Berberine Reduces Chikungunya Virus-Induced Mitogen-Activated Protein Kinase Signaling

Longitudinal [18F]FB-IL-2 PET Imaging to Assess the Immunopathogenicity of O'nyong-nyong Virus Infection

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