Skip to Main content Skip to Navigation
Journal articles

ISG15 Is Critical in the Control of Chikungunya Virus Infection Independent of UbE1L Mediated Conjugation

Abstract : Chikungunya virus (CHIKV) is a re-emerging alphavirus that has caused significant disease in the Indian Ocean region since 2005. During this outbreak, in addition to fever, rash and arthritis, severe cases of CHIKV infection have been observed in infants. Challenging the notion that the innate immune response in infants is immature or defective, we demonstrate that both human infants and neonatal mice generate a robust type I interferon (IFN) response during CHIKV infection that contributes to, but is insufficient for, the complete control of infection. To characterize the mechanism by which type I IFNs control CHIKV infection, we evaluated the role of ISG15 and defined it as a central player in the host response, as neonatal mice lacking ISG15 were profoundly susceptible to CHIKV infection. Surprisingly, UbE1L 2/2 mice, which lack the ISG15 E1 enzyme and therefore are unable to form ISG15 conjugates, displayed no increase in lethality following CHIKV infection, thus pointing to a non-classical role for ISG15. No differences in viral loads were observed between wild-type (WT) and ISG15 2/2 mice, however, a dramatic increase in proinflammatory cytokines and chemokines was observed in ISG15 2/2 mice, suggesting that the innate immune response to CHIKV contributes to their lethality. This study provides new insight into the control of CHIKV infection, and establishes a new model for how ISG15 functions as an immunomodulatory molecule in the blunting of potentially pathologic levels of innate effector molecules during the host response to viral infection.
Document type :
Journal articles
Complete list of metadatas

Cited literature [64 references]  Display  Hide  Download

https://hal-pasteur.archives-ouvertes.fr/pasteur-01402061
Contributor : Marie-Christine Vougny <>
Submitted on : Thursday, November 24, 2016 - 10:59:47 AM
Last modification on : Monday, April 20, 2020 - 2:46:02 PM
Long-term archiving on: : Tuesday, March 21, 2017 - 1:31:50 PM

File

journal.ppat.1002322.PDF
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

Citation

Scott W. Werneke, Clementine Schilte, Anjali Rohatgi, Kristen J. Monte, Alain Michault, et al.. ISG15 Is Critical in the Control of Chikungunya Virus Infection Independent of UbE1L Mediated Conjugation. PLoS Pathogens, Public Library of Science, 2011, 7 (10), pp. e1002322. ⟨10.1371/journal.ppat.1002322⟩. ⟨pasteur-01402061⟩

Share

Metrics

Record views

784

Files downloads

428