Outbreak of Chikungunya Virus Infection, Vanimo, Papua New Guinea

Horwood, Paul F.; Reimer, Lisa J.; Dagina, Rosheila; Susapu, Melinda; Bande, Grace; Katusele, Michelle; Koimbu, Gussy; Jimmy, Stella; Ropa, Berry; Siba, Peter; Pavlin, Boris I

doi:10.3201/eid1909.130130

Cited by 60 publications

(50 citation statements)

References 12 publications

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“…Nucleotide and amino acid identity among the consensus sequences from these individuals was >99.9%. The MCC phylogeny showed that the Dominican Republic sequences clustered within the Asian lineage together with other Caribbean sequences isolated in 2014 [11, 16]. The most closely related Asian sequences circulated between 2012 and 2013 in Micronesia, the Philippines and China.…”

Section: Supporting Informationmentioning

confidence: 99%

Molecular Virologic and Clinical Characteristics of a Chikungunya Fever Outbreak in La Romana, Dominican Republic, 2014

et al. 2016

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Since emerging in Saint Martin in 2013, chikungunya virus (CHIKV), an alphavirus transmitted by the Aedes aegypti mosquito, has infected approximately two million individuals in the Americas, with over 500,000 reported cases in the Dominican Republic (DR). CHIKV-infected patients typically present with a febrile syndrome including polyarthritis/polyarthralgia, and a macropapular rash, similar to those infected with dengue and Zika viruses, and malaria. Nevertheless, many Dominican cases are unconfirmed due to the unavailability and high cost of laboratory testing and the absence of specific treatment for CHIKV infection. To obtain a more accurate representation of chikungunya fever (CHIKF) clinical signs and symptoms, and confirm the viral lineage responsible for the DR CHIKV outbreak, we tested 194 serum samples for CHIKV RNA and IgM antibodies from patients seen in a hospital in La Romana, DR using quantitative RT-PCR and IgM capture ELISA, and performed retrospective chart reviews. RNA and antibodies were detected in 49% and 24.7% of participants, respectively. Sequencing revealed that the CHIKV strain responsible for the La Romana outbreak belonged to the Asian/American lineage and grouped phylogenetically with recent Mexican and Trinidadian isolates. Our study shows that, while CHIKV-infected individuals were infrequently diagnosed with CHIKF, uninfected patients were never falsely diagnosed with CHIKF. Participants testing positive for CHIKV RNA were more likely to present with arthralgia, although it was reported in just 20.0% of CHIKF+ individuals. High percentages of respiratory (19.6%) signs and symptoms, especially among children, were noted, though it was not possible to determine whether individuals infected with CHIKV were co-infected with other pathogens. These results suggest that CHIKV may have been underdiagnosed during this outbreak, and that CHIKF should be included in differential diagnoses of diverse undifferentiated febrile syndromes in the Americas.

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Section: Supporting Informationmentioning

confidence: 99%

Molecular Virologic and Clinical Characteristics of a Chikungunya Fever Outbreak in La Romana, Dominican Republic, 2014

et al. 2016

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“…CHIKV is a re-emerging mosquito-transmitted member of the genus Alphavirus (family Togaviridae) that causes sporadic epidemics of primarily rheumatic disease, with the largest epidemic ever recorded starting in 2004 in Africa and spreading across Asia (Suhrbier et al, 2012), recently reaching Oceania (Horwood et al, 2013) and affecting millions of people. The recent explosive outbreak in the Caribbean (Leparc-Goffart et al, 2014) was the first in the western hemisphere and has even reached the USA (McCarthy, 2014).…”

Section: Introductionmentioning

confidence: 99%

Chikungunya virus non-structural protein 2-mediated host shut-off disables the unfolded protein response

Fros

Major

Scholte

et al. 2015

Journal of General Virology

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The unfolded protein response (UPR) is a cellular defence mechanism against high concentrations of misfolded protein in the endoplasmic reticulum (ER). In the presence of misfolded proteins, ER-transmembrane proteins PERK and IRE1a become activated. PERK phosphorylates eIF2a leading to a general inhibition of cellular translation, whilst the expression of transcription factor ATF4 is upregulated. Active IRE1a splices out an intron from XBP1 mRNA, to produce a potent transcription factor. Activation of the UPR increases the production of several proteins involved in protein folding, degradation and apoptosis. Here, we demonstrated that transient expression of chikungunya virus (CHIKV) (family Togaviridae, genus Alphavirus) envelope glycoproteins induced the UPR and that CHIKV infection resulted in the phosphorylation of eIF2a and partial splicing of XBP1 mRNA. However, infection with CHIKV did not increase the expression of ATF4 and known UPR target genes (GRP78/BiP, GRP94 and CHOP). Moreover, nuclear XBP1 was not observed during CHIKV infection. Even upon stimulation with tunicamycin, the UPR was efficiently inhibited in CHIKV-infected cells. Individual expression of CHIKV nonstructural proteins (nsPs) revealed that nsP2 alone was sufficient to inhibit the UPR. Mutations that rendered nsP2 unable to cause host-cell shut-off prevented nsP2-mediated inhibition of the UPR. This indicates that initial UPR induction takes place in the ER but that expression of functional UPR transcription factors and target genes is efficiently inhibited by CHIKV nsP2.

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“…CHIKV caused an explosive outbreak of disease beginning in 2004 that expanded to areas beyond the historical range of the virus, including Europe and many islands in the Indian Ocean (1,2,13), and produced more-severe illness than previously observed (14)(15)(16)(17). CHIKV continues to spread to new regions (18)(19)(20)(21)(22), and currently there are no available vaccines or treatments for this disease (23).…”

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confidence: 99%

A Single-Amino-Acid Polymorphism in Chikungunya Virus E2 Glycoprotein Influences Glycosaminoglycan Utilization

Silva

Khomandiak

Ashbrook

et al. 2014

J Virol

115

140

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Chikungunya virus (CHIKV) is a reemerging arbovirus responsible for outbreaks of infection throughout Asia and Africa, causing an acute illness characterized by fever, rash, and polyarthralgia. Although CHIKV infects a broad range of host cells, little is known about how CHIKV binds and gains access to the target cell interior. In this study, we tested whether glycosaminoglycan (GAG) binding is required for efficient CHIKV replication using CHIKV vaccine strain 181/25 and clinical isolate SL15649. Preincubation of strain 181/25, but not SL15649, with soluble GAGs resulted in dose-dependent inhibition of infection. While parental Chinese hamster ovary (CHO) cells are permissive for both strains, neither strain efficiently bound to or infected mutant CHO cells devoid of GAG expression. Although GAGs appear to be required for efficient binding of both strains, they exhibit differential requirements for GAGs, as SL15649 readily infected cells that express excess chondroitin sulfate but that are devoid of heparan sulfate, whereas 181/25 did not. We generated a panel of 181/25 and SL15649 variants containing reciprocal amino acid substitutions at positions 82 and 318 in the E2 glycoprotein. Reciprocal exchange at residue 82 resulted in a phenotype switch; Gly 82 results in efficient infection of mutant CHO cells but a decrease in heparin binding, whereas Arg 82 results in reduced infectivity of mutant cells and an increase in heparin binding. These results suggest that E2 residue 82 is a primary determinant of GAG utilization, which likely mediates attenuation of vaccine strain 181/25. IMPORTANCE Chikungunya virus (CHIKV) infection causes a debilitating rheumatic disease that can persist for months to years, and yet there are no licensed vaccines or antiviral therapies. Like other alphaviruses, CHIKV displays broad tissue tropism, which is thought to be influenced by virus-receptor interactions. In this study, we determined that cell-surface glycosaminoglycans are utilized by both a vaccine strain and a clinical isolate of CHIKV to mediate virus binding. We also identified an amino acid polymorphism in the viral E2 attachment protein that influences utilization of glycosaminoglycans. These data enhance an understanding of the viral and host determinants of CHIKV cell entry, which may foster development of new antivirals that act by blocking this key step in viral infection.

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Outbreak of Chikungunya Virus Infection, Vanimo, Papua New Guinea

Cited by 60 publications

References 12 publications

Molecular Virologic and Clinical Characteristics of a Chikungunya Fever Outbreak in La Romana, Dominican Republic, 2014

Molecular Virologic and Clinical Characteristics of a Chikungunya Fever Outbreak in La Romana, Dominican Republic, 2014

Chikungunya virus non-structural protein 2-mediated host shut-off disables the unfolded protein response

A Single-Amino-Acid Polymorphism in Chikungunya Virus E2 Glycoprotein Influences Glycosaminoglycan Utilization

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