Correlation of phylogenetic clade diversification and in vitro infectivity differences among Cosmopolitan genotype strains of Chikungunya virus

Abraham, Rachy; Manakkadan, Anoop; Mudaliar, Prashant; Joseph, Iype; Sivakumar, Krishnankutty C.; Nair, Radhakrishnan R.; Sreekumar, Easwaran

doi:10.1016/j.meegid.2015.11.019

Cited by 23 publications

(24 citation statements)

References 40 publications

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“…Even though this diversity is relatively limited, particularly in the amino acid sequences, notable differences in pathogenesis and virulence between ECSA and Asian lineage isolates have been reported ( 10 , 11 ). Furthermore, individual amino acid substitutions, even between closely related ECSA and IOL lineages, can impact in vitro measures of virulence, such as plaque size, cytopathic effect, and replication kinetics ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

Chikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models

Langsjoen

Haller

Roy

et al. 2018

mBio

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Chikungunya virus (CHIKV) is a reemerging arbovirus capable of causing explosive outbreaks of febrile illness, polyarthritis, and polyarthralgia, inflicting severe morbidity on affected populations. CHIKV can be genetically classified into 3 major lineages: West African (WA); East, Central, and South African (ECSA); Indian Ocean (IOL); and Asian. Additionally, the Indian Ocean (IOL) sublineage emerged within the ECSA clade and the Asian/American sublineage emerged within the Asian clade. While differences in epidemiological and pathological characteristics among outbreaks involving different CHIKV lineages and sublineages have been suggested, few targeted investigations comparing lineage virulence levels have been reported. We compared the virulence levels of CHIKV isolates representing all major lineages and sublineages in the type I interferon receptor-knockout A129 mouse model and found lineage-specific differences in virulence. We also evaluated the cross-protective efficacy of the IOL-derived, live-attenuated vaccine strain CHIKV/IRESv1 against the Asian/American CHIKV isolate YO123223 in both murine and nonhuman primate models, as well as the WA strain SH2830 in a murine model. The CHIKV/IRES vaccine provided protection both in mice and in nonhuman primate cohorts against Caribbean strain challenge and protected mice against WA challenge. Taken together, our data suggest that Asian/American CHIKV strains are less virulent than those in the Asian, ECSA, and WA lineages and that despite differences in virulence, IOL-based vaccine strains offer robust cross-protection against strains from other lineages. Further research is needed to elucidate the genetic basis for variation in CHIKV virulence in the A129 mouse model and to corroborate this variation with human pathogenicity.

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Section: Discussionmentioning

confidence: 99%

Chikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models

Langsjoen

Haller

Roy

et al. 2018

mBio

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“…2008 ; Wasonga et al. 2015 ), India in 2008–2013 ( Abraham et al. 2016 ), and the Caribbean in 2014 ( Sahadeo et al.…”

Section: Discussionmentioning

confidence: 99%

“…2016 ). The function of the nsP1: R171Q mutation has not been described, although nsP1: 171Q variants were shown to have increased cytopathogenicity on primate cells ( Abraham et al. 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Chikungunya virus evolution following a large 3′UTR deletion results in host-specific molecular changes in protein-coding regions

et al. 2018

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The 3′untranslated region (UTR) in alphavirus genomes functions in virus replication and plays a role in determining virus host range. However, the molecular evolution of virus UTRs is understudied compared to the evolution of protein-coding regions. Chikungunya virus (CHIKV) has the longest 3′UTR among the alphaviruses (500–700 nt), and 3′UTR length and sequence structure vary substantially among different CHIKV lineages. Previous studies showed that genomic deletions and insertions are key drivers of CHIKV 3′UTR evolution. Inspired by hypothesized deletion events in the evolutionary history of CHIKV, we used experimental evolution to examine CHIKV adaptation in response to a large 3′UTR deletion. We engineered a CHIKV mutant with a 258 nt deletion in the 3′UTR (ΔDR1/2). This deletion reduced viral replication on mosquito cells, but did not reduce replication on mammalian cells. To examine how selective pressures from vertebrate and invertebrate hosts shape CHIKV evolution after a deletion in the 3′UTR, we passaged ΔDR1/2 virus populations strictly on primate cells, strictly on mosquito cells, or with alternating primate/mosquito cell passages. We found that virus populations passaged on a single host cell line increased in fitness relative to the ancestral deletion mutant on their selected host, and viruses that were alternately passaged improved on both hosts. Surprisingly, whole genome sequencing revealed few changes in the 3′UTR of passaged populations. Rather, virus populations evolved improved fitness through mutations in protein coding regions that were associated with specific hosts.

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“…albopictus adaptive E1:226V mutation was recorded in the province of Kerala (35). Both strains were found circulating in the following years in the country, between 2007 and 2013 (36, 37).…”

Section: Discussionmentioning

confidence: 99%

Recent outbreaks of chikungunya virus (CHIKV) in Africa and Asia are driven by a variant carrying mutations associated with increased fitness for Aedes aegypti

Berry

Eyase

Pollett

et al. 2018

Preprint

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BackgroundIn 2016, a chikungunya virus (CHIKV) outbreak was reported in Mandera, Kenya. This was the first major CHIKV outbreak in the country since the global re-emergence of this virus, which arose as an initial outbreak in Kenya in 2004. Therefore, we collected samples and sequenced viral genomes from the 2016 Mandera outbreak.Methodology/Principal FindingsAll Kenyan genomes contained two mutations, E1:K211E and E2:V264A, recently reported to have an association with increased infectivity, dissemination and transmission in the Aedes aegypti (Ae. aegypti) vector. Phylogeographic inference of temporal and spatial virus relationships using Bayesian approaches showed that this Ae. aegypti adapted strain emerged within the East, Central, and South African (ECSA) lineage of CHIKV between 2005 and 2008, most probably in India. It was also in India where the first large outbreak caused by this strain appeared, in New Delhi, 2010. More importantly, our results also showed that this strain is no longer contained to India, and that it has more recently caused several major outbreaks of CHIKV, including the 2016 outbreaks in India, Pakistan and Kenya, and the 2017 outbreak in Bangladesh. In addition to its capability to cause large outbreaks in different regions of the world, this CHIKV strain has the capacity to replace less adapted wild type strains in Ae. aegypti-rich regions. Indeed, all the latest full CHIKV genomes of the ECSA Indian Ocean Lineage (IOL), from the regions of high Ae. aegypti prevalence, carry these two mutations, including samples collected in Japan, Australia, and China.Conclusions/SignificanceOur results point to the importance of continued genomic-based surveillance of this strain’s global spread, and they prompt urgent vector competence studies in Asian and African countries, in order to assess the level of vector receptiveness, virus transmission, and the impact this might have on this strain’s ability to cause major outbreaks.Author summaryChikungunya virus (CHIKV) causes a debilitating infection with high fever, intense muscle and bone pain, rash, nausea, vomiting and headaches, and persistent and/or recurrent joint pains for months or years after contracting the virus. CHIKV is spread by two mosquito vectors, Aedes albopictus and Aedes aegypti, with increased presence around the globe. In this study, we report global spread of a CHIKV strain that carries two mutations that have been suggested to increase this virus’ ability to infect the Aedes aegypti mosquito, as well as to increase CHIKV’s ability to be transmitted by this vector. We show that this strain appeared sometime between 2005 and 2008, most probably in India, and has now spread to Africa, Asia, and Australia. We show that this strain is capable of driving large outbreaks of CHIKV in the human population, causing recent major outbreaks in Kenya, Pakistan, India and Bangladesh. Thus, our results stress the importance of monitoring this strain’s global spread, as well as the need of improved vector control strategies in the areas of Aedes aegypti prevalence.

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Correlation of phylogenetic clade diversification and in vitro infectivity differences among Cosmopolitan genotype strains of Chikungunya virus

Cited by 23 publications

References 40 publications

Chikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models

Chikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models

Chikungunya virus evolution following a large 3′UTR deletion results in host-specific molecular changes in protein-coding regions

Recent outbreaks of chikungunya virus (CHIKV) in Africa and Asia are driven by a variant carrying mutations associated with increased fitness for Aedes aegypti

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