Chikungunya virus: an update on the biology and pathogenesis of this emerging pathogen

Burt, Felicity J.; Chen, Weiqiang; Miner, Jonathan J.; Lenschow, Deborah J.; Merits, Andres; Schnettler, Esther; Kohl, Alain; Rudd, Penny A.; Taylor, Adam; Herrero, Lara J.; Zaid, Ali; Ng, Lisa F. P.; Mahalingam, Suresh

doi:10.1016/s1473-3099(16)30385-1

Cited by 329 publications

(373 citation statements)

References 154 publications

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“…CHIKV is an alphavirus from the Togaviridae family, which consists of enveloped viruses with a single-stranded, positive-sense RNA genome. CHIKV is also a mosquito-borne virus with a great impact on human health (19). To check if ALFE1 to ALFE3 and AEFE1 transcripts were also capable of generating small RNAs, such as CHIKV-derived viral cDNA, we reanalyzed small RNA libraries from A.…”

Section: Resultsmentioning

confidence: 99%

Uncovering the Repertoire of Endogenous Flaviviral Elements in Aedes Mosquito Genomes

Suzuki

Frangeul

Dickson

et al. 2017

J Virol

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Endogenous viral elements derived from nonretroviral RNA viruses have been described in various animal genomes. Whether they have a biological function, such as host immune protection against related viruses, is a field of intense study. Here, we investigated the repertoire of endogenous flaviviral elements (EFVEs) in Aedes mosquitoes, the vectors of arboviruses such as dengue and chikungunya viruses. Previous studies identified three EFVEs from Aedes albopictus cell lines and one from Aedes aegypti cell lines. However, an in-depth characterization of EFVEs in wild-type mosquito populations and individual mosquitoes in vivo has not been performed. We detected the full-length DNA sequence of the previously described EFVEs and their respective transcripts in several A. albopictus and A. aegypti populations from geographically distinct areas. However, EFVE-derived proteins were not detected by mass spectrometry. Using deep sequencing, we detected the production of PIWI-interacting RNA-like small RNAs, in an antisense orientation, targeting the EFVEs and their flanking regions in vivo. The EFVEs were integrated in repetitive regions of the mosquito genomes, and their flanking sequences varied among mosquito populations. We bioinformatically predicted several new EFVEs from a Vietnamese A. albopictus population and observed variation in the occurrence of those elements among mosquitoes. Phylogenetic analysis of an A. aegypti EFVE suggested that it integrated prior to the global expansion of the species and subsequently diverged among and within populations. The findings of this study together reveal the substantial structural and nucleotide diversity of flaviviral integrations in Aedes genomes. Unraveling this diversity will help to elucidate the potential biological function of these EFVEs.IMPORTANCE Endogenous viral elements (EVEs) are whole or partial viral sequences integrated in host genomes. Interestingly, some EVEs have important functions for host fitness and antiviral defense. Because mosquitoes also have EVEs in their genomes, characterizing these EVEs is a prerequisite for their potential use to manipulate the mosquito antiviral response. In the study described here, we focused on EVEs related to the Flavivirus genus, to which dengue and Zika viruses belong, in individual Aedes mosquitoes from geographically distinct areas. We show the existence in vivo of flaviviral EVEs previously identified in mosquito cell lines, and we detected new ones. We show that EVEs have evolved differently in each mosquito population. They produce transcripts and small RNAs but not proteins, suggesting a function at the RNA level. Our study uncovers the diverse repertoire of flaviviral EVEs in Aedes mosquito populations and contributes to an understanding of their role in the host antiviral system.

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Section: Resultsmentioning

confidence: 99%

Uncovering the Repertoire of Endogenous Flaviviral Elements in Aedes Mosquito Genomes

Suzuki

Frangeul

Dickson

et al. 2017

J Virol

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“…Chikungunya virus infection (CHIKV) is caused by an alphavirus transmitted by Aedes aegypti and Aedes albopictus mosquitoes [1]. Three reports from the mid-1950s describe an outbreak of viral disease observed in the Makonde Plateau of Tanganyika (now in southern Tanzania) in 1952–1953 [2], the environmental and epidemiologic aspects of that outbreak [3] and the virology and other characteristics of the pathogen itself [4].…”

Section: Introductionmentioning

confidence: 99%

Interventions for treating patients with chikungunya virus infection-related rheumatic and musculoskeletal disorders: A systematic review

et al. 2017

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BackgroundChikungunya virus infection (CHIKV) is caused by a mosquito-borne alphavirus. CHIKV causes high fever and painful rheumatic disorders that may persist for years. Because little is known about interventions for treating CHIKV-related illness, we conducted a systematic review.MethodsWe used Cochrane methods. We searched PubMed, EMBASE, Cochrane Library, LILACS and other sources from the earliest records to March 2016. We had no language restrictions. We included randomized controlled trials assessing any intervention for treating acute or chronic CHIKV-related illness. Our primary outcomes were pain relief, global health status (GHS) or health related quality of life (HRQL), and serious adverse events (SAEs). We assessed bias risk with the Cochrane tool and used GRADE to assess evidence quality.ResultsWe screened 2,229 records and found five small trials with a total of 402 participants. Patients receiving chloroquine (CHQ) had better chronic pain relief than those receiving placebo (relative risk [RR] 2.67, 95% confidence interval [CI] 1.23 to 5.77, N = 54), but acute pain relief was marginally not different between groups (mean difference [MD] 1.46, 95% CI 0.00 to 2.92, N = 54). SAEs were similar (RR = 15.00, 95% CI 0.90 to 250.24, N = 54). Comparing CHQ with paracetamol (PCM), CHQ patients had better pain relief (RR = 1.52, 95% CI 1.20 to 1.93, N = 86). Compared with hydroxychloroquine (HCHQ), disease-modifying anti-rheumatic drugs (DMARDs) reduced pain (MD = -14.80, 95% CI -19.12 to -10.48, N = 72). DMARDs patients had less disability (MD = -0.74, 95% CI -0.92 to -0.56, N = 72) and less disease activity (MD = -1.35; 95% CI -1.70 to -1.00; N = 72). SAEs were similar between DMARDs and HCHQ groups (RR = 2.84, 95% CI 0.12 to 67.53, N = 72). Comparing meloxicam (MXM) with CHQ, there was no difference in pain relief (MD = 0.24, 95% CI = -0.81 to 1.29; p = 0.65, N = 70), GHS or HRQL (MD = -0.31, 95% CI -2.06 to 1.44, N = 70) or SAEs (RR = 0.85, 95% CI 0.30 to 2.42, N = 70). Finally, a four-arm trial (N = 120) compared aceclofenac (ACF) monotherapy to ACF+HCHQ, ACF+ prednisolone (PRD), or ACF+HCHQ+PRD. Investigators found reduced pain (p<0.001) and better HRQL (p<0.001) in the two patient groups receiving PRD, compared to those receiving ACF monotherapy or ACF+HCHQ. Trials were at high risk of bias. GRADE evidence quality for all outcomes was very low.ConclusionResults from these small trials provide insufficient evidence to draw conclusions about the efficacy or safety of CHIKV interventions. Physicians should be cautious in prescribing and policy-makers should be cautious in recommending any intervention reviewed here. Rigorous trials with sufficient statistical power are urgently needed, with results stratified by disease stage and symptomology.

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“…CHIKV had been confined to Africa and Asia, but in the past decade, the virus has spread to the western hemisphere to cause widespread epidemics (Burt et al, 2017). The typical vector responsible for transmission of CHIKV was Aedes aegypti , but a mutation in the viral envelope led to enhanced replication in the Aedes albopictus mosquitos present in temperate regions, potentially expanding the range of transmission (Tsetsarkin et al, 2007).…”

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confidence: 99%

A potent prolyl tRNA synthetase inhibitor antagonizes Chikungunya and Dengue viruses

2019

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Arboviruses represent a group of pathogens that can spread efficiently throughout human populations by hematophagous arthropod vectors. The mosquito-borne (re)emerging Chikungunya and Dengue viruses belong to the alphavirus and flavivirus genus, respectively, with no approved therapeutics or safe vaccines for humans. Transmitted by the same vector Aedes spp., these viruses cause significant morbidity and mortality in endemic areas. Due to the increasing likelihood of co-circulation and co-infection with viruses, we aimed to identify a pharmacologically targetable host factor that can inhibit multiple viruses and show that a potent antagonist of prolyl tRNA synthetase (halofuginone) suppresses both Chikungunya and Dengue viruses. Host tRNA synthetase inhibition may signify an additional approach to combat present and future epidemic pathogens.

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Chikungunya virus: an update on the biology and pathogenesis of this emerging pathogen

Cited by 329 publications

References 154 publications

Uncovering the Repertoire of Endogenous Flaviviral Elements in Aedes Mosquito Genomes

Uncovering the Repertoire of Endogenous Flaviviral Elements in Aedes Mosquito Genomes

Interventions for treating patients with chikungunya virus infection-related rheumatic and musculoskeletal disorders: A systematic review

A potent prolyl tRNA synthetase inhibitor antagonizes Chikungunya and Dengue viruses

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