Distinguishing Secondary Dengue Virus Infection From Zika Virus Infection With Previous Dengue by a Combination of 3 Simple Serological Tests

ABSTRACT Zika virus (ZIKV) is an emerging flavivirus that can cause birth defects and neurologic complications. Molecular tests are effective for diagnosing acute ZIKV infection, although the majority of infections produce no symptoms at all or present after the narrow window in which molecular diagnostics are dependable. Serology is a reliable method for detecting infections after the viremic period; however, most serological assays have limited specificity due to cross-reactive antibodies elicited by flavivirus infections. Since ZIKV and dengue virus (DENV) widely cocirculate, distinguishing ZIKV infection from DENV infection is particularly important for diagnosing individual cases or for surveillance to coordinate public health responses. Flaviviruses also elicit type-specific antibodies directed to non-cross-reactive epitopes of the infecting virus; such epitopes are attractive targets for the design of antigens for development of serological tests with greater specificity. Guided by comparative epitope modeling of the ZIKV envelope protein, we designed two recombinant antigens displaying unique antigenic regions on domain I (Z-EDI) and domain III (Z-EDIII) of the ZIKV envelope protein. Both the Z-EDI and Z-EDIII antigens consistently detected ZIKV-specific IgG in ZIKV-immune sera but not cross-reactive IgG in DENV-immune sera in late convalescence (>12 weeks postinfection). In contrast, during early convalescence (2 to 12 weeks postinfection), secondary DENV-immune sera and some primary DENV-immune sera cross-reacted with the Z-EDI and Z-EDIII antigens. Analysis of sequential samples from DENV-immune individuals demonstrated that Z-EDIII cross-reactivity peaked in early convalescence and declined steeply over time. The Z-EDIII antigen has much potential as a diagnostic antigen for population-level surveillance and for detecting past infections in patients.

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Zika virus infection in a traveller returning to Europe from Brazil, March 2015

Eurosurveillance ◽

10.2807/1560-7917.es2015.20.23.21153 ◽

2015 ◽

Vol 20 (23) ◽

Cited By ~ 84

Author(s):

L Zammarchi ◽

D Tappe ◽

C Fortuna ◽

M E Remoli ◽

S Günther ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Zika Virus ◽

Chikungunya Virus ◽

Healthcare Systems ◽

Mosquito Vectors ◽

Zika Virus Infection ◽

Hands And Feet

We report a case of laboratory-confirmed Zika virus infection imported into Europe from the Americas. The patient developed fever, rash, and oedema of hands and feet after returning to Italy from Brazil in late March 2015. The case highlights that, together with chikungunya virus and dengue virus, three major arboviruses are now co-circulating in Brazil. These arboviruses represent a burden for the healthcare systems in Brazil and other countries where competent mosquito vectors are present.

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Longitudinal Analysis of Antibody Cross-neutralization Following Zika Virus and Dengue Virus Infection in Asia and the Americas

The Journal of Infectious Diseases ◽

10.1093/infdis/jiy164 ◽

2018 ◽

Vol 218 (4) ◽

pp. 536-545 ◽

Cited By ~ 69

Author(s):

Magelda Montoya ◽

Matthew Collins ◽

Wanwisa Dejnirattisai ◽

Leah C Katzelnick ◽

Henry Puerta-Guardo ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Longitudinal Analysis ◽

Zika Virus ◽

Dengue Virus Infection ◽

Cross Neutralization

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Zika virus infection in human placental tissue explants is enhanced in the presence of dengue virus antibodies in-vitro

Emerging Microbes & Infections ◽

10.1038/s41426-018-0199-6 ◽

2018 ◽

Vol 7 (1) ◽

pp. 1-8 ◽

Cited By ~ 17

Author(s):

Kyra Hermanns ◽

Claudia Göhner ◽

Anne Kopp ◽

Andre Schmidt ◽

Waltraut M. Merz ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Zika Virus ◽

Placental Tissue ◽

Tissue Explants ◽

Zika Virus Infection ◽

Human Placental Tissue

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Cross-Reactive Dengue Virus Antibodies Augment Zika Virus Infection of Human Placental Macrophages

Cell Host & Microbe ◽

10.1016/j.chom.2018.10.008 ◽

2018 ◽

Vol 24 (5) ◽

pp. 731-742.e6 ◽

Cited By ~ 52

Author(s):

Matthew G. Zimmerman ◽

Kendra M. Quicke ◽

Justin T. O'Neal ◽

Nitin Arora ◽

Deepa Machiah ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Zika Virus ◽

Zika Virus Infection ◽

Placental Macrophages

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Global Transcriptome Analysis of Aedes aegypti Mosquitoes in Response to Zika Virus Infection

mSphere ◽

10.1128/msphere.00456-17 ◽

2017 ◽

Vol 2 (6) ◽

Cited By ~ 30

Author(s):

Kayvan Etebari ◽

Shivanand Hegde ◽

Miguel A. Saldaña ◽

Steven G. Widen ◽

Thomas G. Wood ◽

...

Keyword(s):

Virus Infection ◽

Aedes Aegypti ◽

Dengue Virus ◽

Zika Virus ◽

Virus Transmission ◽

Noncoding Rnas ◽

Transcriptional Response ◽

Mosquito Vector ◽

Content Type ◽

Zika Virus Infection

ABSTRACT Vector-borne viruses pose great risks to human health. Zika virus has recently emerged as a global threat, rapidly expanding its distribution. Understanding the interactions of the virus with mosquito vectors at the molecular level is vital for devising new approaches in inhibiting virus transmission. In this study, we embarked on analyzing the transcriptional response of Aedes aegypti mosquitoes to Zika virus infection. Results showed large changes in both coding and long noncoding RNAs. Analysis of these genes showed similarities with other flaviviruses, including dengue virus, which is transmitted by the same mosquito vector. The outcomes provide a global picture of changes in the mosquito vector in response to Zika virus infection. Zika virus (ZIKV) of the Flaviviridae family is a recently emerged mosquito-borne virus that has been implicated in the surge of the number of microcephaly instances in South America. The recent rapid spread of the virus led to its declaration as a global health emergency by the World Health Organization. The virus is transmitted mainly by the mosquito Aedes aegypti, which is also the vector of dengue virus; however, little is known about the interactions of the virus with the mosquito vector. In this study, we investigated the transcriptome profiles of whole A. aegypti mosquitoes in response to ZIKV infection at 2, 7, and 14 days postinfection using transcriptome sequencing. Results showed changes in the abundance of a large number of transcripts at each time point following infection, with 18 transcripts commonly changed among the three time points. Gene ontology analysis revealed that most of the altered genes are involved in metabolic processes, cellular processes, and proteolysis. In addition, 486 long intergenic noncoding RNAs that were altered upon ZIKV infection were identified. Further, we found changes of a number of potential mRNA target genes correlating with those of altered host microRNAs. The outcomes provide a basic understanding of A. aegypti responses to ZIKV and help to determine host factors involved in replication or mosquito host antiviral response against the virus. IMPORTANCE Vector-borne viruses pose great risks to human health. Zika virus has recently emerged as a global threat, rapidly expanding its distribution. Understanding the interactions of the virus with mosquito vectors at the molecular level is vital for devising new approaches in inhibiting virus transmission. In this study, we embarked on analyzing the transcriptional response of Aedes aegypti mosquitoes to Zika virus infection. Results showed large changes in both coding and long noncoding RNAs. Analysis of these genes showed similarities with other flaviviruses, including dengue virus, which is transmitted by the same mosquito vector. The outcomes provide a global picture of changes in the mosquito vector in response to Zika virus infection.

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Global transcriptome analysis of Aedes aegypti mosquitoes in response to Zika virus infection

10.1101/179416 ◽

2017 ◽

Cited By ~ 1

Author(s):

Kayvan Etebari ◽

Shivanand Hegde ◽

Miguel A Saldaña ◽

Steven G Widen ◽

Thomas G Wood ◽

...

Keyword(s):

Virus Infection ◽

Aedes Aegypti ◽

Dengue Virus ◽

Zika Virus ◽

Target Genes ◽

World Health ◽

Mosquito Vector ◽

Zikv Infection ◽

Zika Virus Infection ◽

Non Coding Rnas

AbstractZika virus (ZIKV) of the Flaviviridae family is a recently emerged mosquito-borne virus that has been implicated in the surge of the number of microcephaly instances in South America. The recent rapid spread of the virus led to its declaration as a global health emergency by the World Health Organization. The virus is transmitted mainly by the mosquito Aedes aegypti that also vectors dengue virus, however little is known about the interactions of the virus with the mosquito vector. In this study, we investigated the transcriptome profiles of whole Ae. aegypti mosquitoes in response to ZIKV infection at 2, 7, and 14 days post-infection using RNA-Seq. Results showed changes in the abundance of a large number of transcripts at each time point following infection, with 18 transcripts commonly changed among the three time points. Gene ontology analysis revealed that most of the altered genes are involved in metabolic process, cellular process and proteolysis. In addition, 486 long intergenic non-coding RNAs were identified that were altered upon ZIKV infection. Further, we found correlational changes of a number of potential mRNA target genes with that of altered host microRNAs. The outcomes provide a basic understanding of Ae. aegypti responses to ZIKV and helps to determine host factors involved in replication or mosquito host anti-viral response against the virus.ImportanceVector-borne viruses pose great risks on human health. Zika virus has recently emerged as a global threat, rapidly expanding its distribution. Understanding the interactions of the virus with mosquito vectors at the molecular level is vital for devising new approaches in inhibiting virus transmission. In this study, we embarked on analyzing the transcriptional response of Aedes aegypti mosquitoes to Zika virus infection. Results showed large changes both in coding and long non-coding RNAs. Analysis of these genes showed similarities with other flaviviruses, including dengue virus, which is transmitted by the same mosquito vector. The outcomes provide a global picture of changes in the mosquito vector in response to Zika virus infection.

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