Chikungunya virus infection

Abstract

Chikungunya virus (CHIKV) belongs to the "old world" Alphavirus family and is an arbovirus transmitted by Aedes mosquitoes. It is a tropical disease originally described in central/east Africa in the 1950s, but the recent re-emergence from2004 in Africa and rapid spread in and around the Indian Ocean (Reunion island, India, Malaysia) as well as Europe (Italy) led to several millions of cases with unprecedented neurological complications.Recent epidemics in 2005-2008 have revealed that there is a high titer viremia and that CHIKV can gain access to the brain in susceptible hosts such as neonates and elderly patientswith comorbidities (chronic disease of liver, heart, and kidneys). New mutated forms were identified in the recent outbreaks, but their contribution to severe pathologies is only speculative at this stage. Classically, CHIKV causes an acute symptomatic illness over a period of 5-7 dayswith fever, skin rash, and incapacitating arthralgias, and can evolve into chronic rheumatoid arthritis-like diseases, particularly in elderly patients. CHIKV infection can also lead to severe meningoencephalitis, encephalitis with white matter lesions, peripheral neuropathies, optic neuritis, and death. In neonates central nervous system (CNS) infection can lead to long-term sequelae. The early and robust systemic innate and adaptive immune responses are able to protect the host. However, the virus has been shown to persist in tissue sanctuaries months after the initial infection in humans and animal models. In the brain, CHIKV preferentially targets astrocytes, ependymal cells, epithelial cells of the choroid plexus, and neurons. The route and themechanisms involved in neuroinfection, the antiviral response mounted by resident cells and neuroinflammation are largely illcharacterized. CHIKV may critically polarize host-cell defense mechanisms such as IFN signaling pathway, apoptosis, and autophagy to its own advantage and studies to decipher the molecular mechanisms of immune escape are now highly warranted.