Genome Microevolution of Chikungunya Viruses Causing the Indian Ocean Outbreak

Abstract

BackgroundA chikungunya virus outbreak of unprecedented magnitude is currently ongoing in Indian Ocean territories. In Réunion Island, this alphavirus has already infected about one-third of the human population. The main clinical symptom of the disease is a painful and invalidating poly-arthralgia. Besides the arthralgic form, 123 patients with a confirmed chikungunya infection have developed severe clinical signs, i.e., neurological signs or fulminant hepatitis.Methods and FindingsWe report the nearly complete genome sequence of six selected viral isolates (isolated from five sera and one cerebrospinal fluid), along with partial sequences of glycoprotein E1 from a total of 127 patients from Réunion, Seychelles, Mauritius, Madagascar, and Mayotte islands. Our results indicate that the outbreak was initiated by a strain related to East-African isolates, from which viral variants have evolved following a traceable microevolution history. Unique molecular features of the outbreak isolates were identified. Notably, in the region coding for the non-structural proteins, ten amino acid changes were found, four of which were located in alphavirus-conserved positions of nsP2 (which contains helicase, protease, and RNA triphosphatase activities) and of the polymerase nsP4. The sole isolate obtained from the cerebrospinal fluid showed unique changes in nsP1 (T301I), nsP2 (Y642N), and nsP3 (E460 deletion), not obtained from isolates from sera. In the structural proteins region, two noteworthy changes (A226V and D284E) were observed in the membrane fusion glycoprotein E1. Homology 3D modelling allowed mapping of these two changes to regions that are important for membrane fusion and virion assembly. Change E1-A226V was absent in the initial strains but was observed in >90% of subsequent viral sequences from Réunion, denoting evolutionary success possibly due to adaptation to the mosquito vector.ConclusionsThe unique molecular features of the analyzed Indian Ocean isolates of chikungunya virus demonstrate their high evolutionary potential and suggest possible clues for understanding the atypical magnitude and virulence of this outbreak.

Atypical Chikungunya virus infections: clinical manifestations, mortality and risk factors for severe disease during the 2005–2006 outbreak on Réunion

“…Alternatively, the fact that the outbreak occurred on an island with European health standards may have increased the chance of identifying and documenting such events [1]. On the other hand, the spread of Chikungunya virus during the outbreak on Re´union was found to have novel molecular features, which may have led to its increased virulence [18,19]. During the 2005 outbreak, the incidence of atypical infections on Re´union was 0 .…”

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

“…Therefore, I211T destabilized and G82R stabilized the three dimensional structure of the E2 protein. A large epidemic of CHIKV occurred in 2004-2009 in the Indian Ocean region affecting millions of people [33]. A point mutation in the E1 protein (A226V) was identified in most of the virus isolates of this epidemic.…”

Expression of the capsid protein of Chikungunya virus in a baculovirus for serodiagnosis of Chikungunya disease

“…Ross during an outbreak of dengue-like fever in Tanzania, East Africa in 1952 (Ross, 1956). During 2005During -2006, an epidemic outbreak of CHIK fever occurred on several islands in the Indian Ocean and in India, resulting in millions of clinically suspected cases (Mavalankar et al, 2007;Schuffenecker et al, 2006). In 2006, there was a major outbreak of CHIKV infection in India with 1.39 million reported cases (Lahariya and Pradhan, 2006).…”