Early Events in Chikungunya Virus Infection—From Virus CellBinding to Membrane Fusion

Abstract

Chikungunya virus (CHIKV) is a rapidly emerging mosquito-borne alphavirus causing millions of infections in the tropical and subtropical regions of the world. CHIKV infection often leads to an acute self-limited febrile illness with debilitating myalgia and arthralgia. A potential long-term complication of CHIKV infection is severe joint pain, which can last for months to years. There are no vaccines or specific therapeutics available to prevent or treat infection. This review describes the critical steps in CHIKV cell entry. We summarize the latest studies on the virus-cell tropism, virus-receptor binding, internalization, membrane fusion and review the molecules and compounds that have been described to interfere with virus cell entry. The aim of the review is to give the reader a state-of-the-art overview on CHIKV cell entry and to provide an outlook on potential new avenues in CHIKV research.

Potential entry inhibitors of the envelope protein (E2) of Chikungunya virus: in silico structural modeling, docking and molecular dynamic studies

“…Further, they also concluded that Fig. 3 The secondary structure of E2 protein generated using the Psipred server Potential entry inhibitors of the envelope protein (E2) of Chikungunya virus: in silico… 43 this mutation at 211 position is probably involved in binding of the E2 protein with the receptor on the host cell [41]. Glycosaminoglycans (GAGs) are polymers of disaccharide units that are associated with the outer surface of mammalian cells where they act as virus receptors.…”

“…Both CHIKV and DENV are spread by Aedes aegypti and Aedes albopictus mosquitoes [3]. CHIKV is endemic in many parts of the world including Africa, Asia and tropical regions of America [43]. Nearly 94 countries were identified with substantial CHIKV infection in a recent investigation [26].…”

“…It was also estimated that around 1.3 billion people are living in risk areas for CHIKV transmission [26]. The CHIKV has been reported from more than 40 countries in the Americas with over 1 million infections in last 2 years [43]. The largest outbreak of CHIKV occurred during [2004][2005][2006][2007][2008][2009] in Indian Ocean region involving millions of people [41].…”

Chikungunya: Molecular Aspects, Clinical Outcomes and Pathogenesis

“…3). With less frequency, the virus can affect the liver or cause encephalopathy, encephalitis, myocarditis, and heart blockage 27 . Although 5-15% of individuals suffer from asymptomatic infection 26 , the rest generally develop symptoms that progress from the acute to the chronic phase 25 .…”

“…Chronic symptomatology is observed with greater frequency in persons over 60 years of age that have very high viremia (> 10 10 PFU/ml) during the acute phase of the disease 27 . The infection is initially very rapid and the virus is typically eliminated 5-7 days after onset of the fever.…”