Diagnosis of Zika virus infection on a nanotechnology platform

Zhang, Bo; Pinsky, Benjamin A.; Ananta, Jeyarama S.; Zhao, Su; Arulkumar, Shylaja; Wan, Hao; Sahoo, Malaya K.; Abeynayake, Janaki; Waggoner, Jesse J.; Hopes, Clay; Tang, Meijie; Dai, Hongjie

doi:10.1038/nm.4302

Cited by 140 publications

(133 citation statements)

References 15 publications

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“…Detection of viral RNA in urine and saliva has become an important diagnostic tool for ZIKV. The value of IgA response for ZIKV infection in serum has been reported . But it has not been reported whether ZIKV‐specific IgA antibody could by detected in urine and saliva.…”

Section: Discussionmentioning

confidence: 99%

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Kinetics of antigen‐specific IgM/IgG/IgA antibody responses during Zika virus natural infection in two patients

Zhao

Hong

Wang

et al. 2018

Journal of Medical Virology

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Understanding of kinetics of antibody responses is crucial for developing rapid serological tests and studying the mechanisms of Zika virus (ZIKV) infection. Most of the serological diagnostic assays previously published are based on either IgM or IgG titer, little is known on the level of IgA antibody in saliva and urine. In this study, we investigated the kinetics of IgM/IgG/IgA antibody responses in serum, saliva, and urine obtained from two ZIKV infected individuals from as early as the second day of onset of symptoms to as long as 2 years postinfection. Other than detecting robust early IgM response, long lasting IgG response, we discovered strong early IgA response specific for ZIKV in saliva in both patients. This unique observation provides a novel strategy and scientific basis for the development of noninvasive rapid tests for ZIKV infection.

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Section: Discussionmentioning

confidence: 99%

“…The value of IgA response for ZIKV infection in serum has been reported. 16,17 But it has not been reported whether ZIKV-specific IgA antibody could by detected in urine and saliva. In this study, we found that anti-ZIKV IgA could be detected in saliva collected during acute stage and early convalescent phase of infection, but not in urine.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of antigen‐specific IgM/IgG/IgA antibody responses during Zika virus natural infection in two patients

Zhao

Hong

Wang

et al. 2018

Journal of Medical Virology

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“…A multiplex microsphere immunoassay using DENV and ZIKV E, NS1, and NS5 proteins was shown to improve diagnostic accuracy (Wong et al, 2017). More recently a nanotechnology platform has been developed to detect IgG avidity against the NS1 protein of the ZIKV and this has been submitted to the FDA for EUA (Zhang et al, 2017). …”

Section: Current Status Of Diagnostic Testing (Diogo M Magnani Mmentioning

confidence: 99%

Zika in the Americas, year 2: What have we learned? What gaps remain? A report from the Global Virus Network

et al. 2017

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In response to the outbreak of Zika virus (ZIKV) infection in the Western Hemisphere and the recognition of a causal association with fetal malformations, the Global Virus Network (GVN) assembled an international taskforce of virologists to promote basic research, recommend public health measures and encourage the rapid development of vaccines, antiviral therapies and new diagnostic tests. In this article, taskforce members and other experts review what has been learned about ZIKV-induced disease in humans, its modes of transmission and the cause and nature of associated congenital manifestations. After describing the make-up of the taskforce, we summarize the emergence of ZIKV in the Americas, Africa and Asia, its spread by mosquitoes, and current control measures. We then review the spectrum of primary ZIKV-induced disease in adults and children, sites of persistent infection and sexual transmission, then examine what has been learned about maternal-fetal transmission and the congenital Zika syndrome, including knowledge obtained from studies in laboratory animals. Subsequent sections focus on vaccine development, antiviral therapeutics and new diagnostic tests. After reviewing current understanding of the mechanisms of emergence of Zika virus, we consider the likely future of the pandemic.

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“…qRT-PCR [24] and serological assays confirmed the diagnosis of DENV infection and excluded other arboviral infections (including Zika and chikungunya) [25] . IgG avidity testing distinguished primary from secondary dengue ( Supplementary Table 1) [25] . PBMC samples were isolated, stored and shipped in liquid nitrogen.…”

Section: High-dimensional Profiling Of Single Cells From Dengue Virusmentioning

confidence: 79%

Virus-inclusive single cell RNA sequencing reveals molecular signature predictive of progression to severe dengue infection

Zanini

Croote

et al. 2018

Preprint

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Dengue virus (DENV) infection can result in severe complications. Yet, the understanding of the molecular correlates of severity is limited, partly due to difficulties in defining the peripheral blood mononuclear cells (PBMCs) that are associated with DENV in vivo. Additionally, t here are currently no biomarkers predictive of progression to severe dengue (SD) . Bulk transcriptomics data are difficult to interpret because blood consists of multiple cell types that may react differently to infection. Here we applied virus-inclusive single cell RNA-seq approach (viscRNA-Seq) to profile transcriptomes of thousands of single PBMCs derived early in the course of disease from six dengue patients and four healthy controls, and to characterize distinct DENV-associated leukocytes. Multiple genes, particularly interferon response genes, were upregulated in a cell-specific manner prior to progression to SD. Expression of MX2 in naive B cells and CD163 in CD14 + CD16 + monocytes was predictive of SD. The majority of DENV-associated cells in the blood of two patients who progressed to SD were naive IgM B cells expressing the CD69 and CXCR4 receptors and antiviral genes, followed by monocytes.Bystander uninfected B cells also demonstrated immune activation, and plasmablasts from two patients exhibited antibody lineages with convergently hypermutated heavy chain sequences. Lastly, assembly of the DENV genome revealed diversity at unexpected genomic sites. This study presents a multi-faceted molecular elucidation of natural dengue infection in humans and proposes biomarkers for prediction of SD, with implications for profiling any tissue and viral infection, and for the development of a dengue prognostic assay. SignificanceA fraction of the 400 million people infected with dengue annually progresses to severe dengue (SD). Yet, there are currently no biomarkers to effectively predict disease progression. We profiled the landscape of host transcripts and viral RNA in thousands of single blood cells from dengue patients prior to progressing to SD. We discovered cell-type specific immune activation and candidate predictive biomarkers. We also revealed preferential virus association with specific cell populations, particularly naive B cells and monocytes. We then explored immune activation of bystander cells, clonality and somatic evolution of adaptive immune repertoires, and viral genomics. This multi-faceted approach could advance understanding of pathogenesis of any viral infection, map an atlas of infected cells and promote the development of prognostics.

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Diagnosis of Zika virus infection on a nanotechnology platform

Cited by 140 publications

References 15 publications

Kinetics of antigen‐specific IgM/IgG/IgA antibody responses during Zika virus natural infection in two patients

Kinetics of antigen‐specific IgM/IgG/IgA antibody responses during Zika virus natural infection in two patients

Zika in the Americas, year 2: What have we learned? What gaps remain? A report from the Global Virus Network

Virus-inclusive single cell RNA sequencing reveals molecular signature predictive of progression to severe dengue infection

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