Spread of a Novel Indian Ocean Lineage Carrying E1-K211E/E2-V264A of Chikungunya Virus East/Central/South African Genotype across the Indian Subcontinent, Southeast Asia, and Eastern Africa

Abstract

The Indian Ocean Lineage (IOL) of the chikungunya virus (CHIKV) East/Central/South African (ECSA) genotype, which originated in Kenya, spread to the Indian ocean and the Indian subcontinent, and then expanded through Southeast Asia in the previous decade. It carried an adaptive mutation E1-A226V, which enhances CHIKV replication in Aedes albopictus. However, the IOL CHIKV of the most recent outbreaks during 2016–2020 in India, Pakistan, Bangladesh, the Maldives, Myanmar, Thailand, and Kenya lacked E1-A226V but carried E1-K211E and E2-V264A. Recent CHIKV genome sequences of the Maldives and Thailand were determined, and their phylogenetic relationships were further investigated together with IOL sequences reported in 2004–2020 in the database. The results showed that the ancestral IOLs diverged to a sub-lineage E1-K211E/E2-V264A, probably in India around 2008, and caused sporadic outbreaks in India during 2010–2015 and in Kenya in 2016. The massive expansion of this new sub-lineage occurred after the acquisition of E1-I317V in other neighboring and remote regions in 2014–2020. Additionally, the phylogenetic tree indicated that independent clades formed according to the geographical regions and introduction timing. The present results using all available partial or full sequences of the recent CHIKVs emphasized the dynamics of the IOL sub-lineages in the Indian subcontinent, Southeast Asia, and Eastern Africa.

The evolutionary and molecular history of a chikungunya virus outbreak lineage

“…1). The last common ancestor of the IOL of the ECSA genotype is estimated to have originated in coastal Kenya and the Mascarene islands, around early 2003 (95% HPD: 2001-07–2004-02), which is consistent with previous estimates [50, 55]. A new IOL sub-lineage, distinct from the previous IOL that originated from the Kenyan coast, was found to have originated in India and circulated during 2008–2016, with subsequent spread to Pakistan, Bangladesh, Thailand, and Italy [56].…”

“…Here we examine the evolutionary history of CHIKV to trace the origins of the outbreak lineage that caused a substantial number of cases in Thailand and other Southeast Asian countries in 2018 and 2019 [24, 26]. The 2004 outbreak of CHIKV in the Indian Ocean islands was the first documented outbreak in the IOL [50]. The outbreak was mainly observed in urban and semi-urban areas, for example on the Comoros Islands where more than 5,000 cases were reported [51].…”

Chikungunya in Zhejiang Province, Southeast China

“…Virus evolution and importation of novel virus strain are the important drivers for the emergence and reemergence of chikungunya [26] . IOL CHIKV, which carrying an alanine-to-valine mutation at position 226 within the E1 glycoprotein (E1-A226V), was responsible for a series of outbreaks in Kenya, the Indian ocean, the Indian subcontinent and Southeast Asia in the previous decade [ 26 , 27 ]. The adaptive mutation E1-A226V was proved to enhance CHIKV replication in Aedes albopictus , which render the wide spread of CHIKV in the region abundant with this mosquito.…”

Broad-spectrum antiviral inhibitors targeting pandemic potential RNA viruses

“…Given their already-demonstrated epidemic potential, finding effective broad-spectrum treatments against these viruses is of the utmost importance as they become potential agents for pandemics. Mutations in the CHIKV Envelope gene (e.g., E1-A226V, E1-K211E, E2-V264A, E1-I317V) 11,12 , particularly in the Indian Ocean Lineage of the virus, have significantly increased CHIKV adaptability and infectivity. Understanding CHIKV is particularly important because it has already shown the potential to spread like wildfire in the event of even one of these mutations, particularly the E1-A226V adaptive mutation which improved viral replication and transmission efficiency.…”

“…Understanding CHIKV is particularly important because it has already shown the potential to spread like wildfire in the event of even one of these mutations, particularly the E1-A226V adaptive mutation which improved viral replication and transmission efficiency. We have seen the impact of these CHIKV mutations in epidemics and mass outbreaks in Eastern Africa 12 , South 13 and Southeast Asia 14 , and South America 15 . South America, having served as a hotbed for the spread of a new variant of ZIKV in 2016 16 , knows the impact that these viruses can have in terms of rapid spread and overwhelming medical infrastructure and public health efforts.…”