Diagnosis of Zika Virus Infection by Peptide Array and Enzyme-Linked Immunosorbent Assay
ABSTRACT Zika virus (ZIKV) is implicated in fetal stillbirth, microcephaly, intracranial calcifications, and ocular anomalies following vertical transmission from infected mothers. In adults, infection may trigger autoimmune inflammatory polyneuropathy. Transmission most commonly follows the bite of...
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American Society for Microbiology
2018
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oai:doaj.org-article:b09d562b006747a79f5be39b615d36032021-11-15T15:53:26ZDiagnosis of Zika Virus Infection by Peptide Array and Enzyme-Linked Immunosorbent Assay10.1128/mBio.00095-182150-7511https://doaj.org/article/b09d562b006747a79f5be39b615d36032018-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00095-18https://doaj.org/toc/2150-7511ABSTRACT Zika virus (ZIKV) is implicated in fetal stillbirth, microcephaly, intracranial calcifications, and ocular anomalies following vertical transmission from infected mothers. In adults, infection may trigger autoimmune inflammatory polyneuropathy. Transmission most commonly follows the bite of infected Aedes mosquitoes but may also occur through sexual intercourse or receipt of blood products. Definitive diagnosis through detection of viral RNA is possible in serum or plasma within 10 days of disease onset, in whole blood within 3 weeks of onset, and in semen for up to 3 months. Serological diagnosis is nonetheless critical because few patients have access to molecular diagnostics during the acute phase of infection and infection may be associated with only mild or inapparent disease that does not prompt molecular testing. Serological diagnosis is confounded by cross-reactivity of immune sera with other flaviviruses endemic in the areas where ZIKV has recently emerged. Accordingly, we built a high-density microarray comprising nonredundant 12-mer peptides that tile, with one-residue overlap, the proteomes of Zika, dengue, yellow fever, West Nile, Ilheus, Oropouche, and chikungunya viruses. Serological analysis enabled discovery of a ZIKV NS2B 20-residue peptide that had high sensitivity (96.0%) and specificity (95.9%) versus natural infection with or vaccination against dengue, chikungunya, yellow fever, West Nile, tick-borne encephalitis, or Japanese encephalitis virus in a microarray assay and an enzyme-linked immunosorbent assay (ELISA) of early-convalescent-phase sera (2 to 3 weeks after onset of symptomatic infection). IMPORTANCE The emergence of Zika virus (ZIKV) as a teratogen is a profound challenge to global public health. Molecular diagnosis of infection is straightforward during the 3-week period when patients are viremic. However, serological diagnosis thereafter of historical exposure has been confounded by cross-reactivity. Using high-density peptide arrays that tile the proteomes of a selection of flaviviruses to identify a ZIKV-specific peptide, we established two assays that enable sensitive and specific diagnosis of exposure to ZIKV. These assays may be useful in guiding clinical management of mothers at risk for potential exposure to ZIKV and enable insights into the epidemiology of ZIKV infections.Nischay MishraAdrian CaciulaAdam PriceRiddhi ThakkarJames NgLokendra V. ChauhanKomal JainXiaoyu CheDiego A. EspinosaMagelda Montoya CruzAngel BalmasedaEric H. SullivanJigar J. PatelRichard G. JarmanJennifer L. RakemanChristina T. EganChantal B. E. M. ReuskenMarion P. G. KoopmansEva HarrisRafal TokarzThomas BrieseW. Ian LipkinAmerican Society for Microbiologyarticlearbovirusemerging infectious diseasesflavivirusserologyZikaMicrobiologyQR1-502ENmBio, Vol 9, Iss 2 (2018) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
arbovirus emerging infectious diseases flavivirus serology Zika Microbiology QR1-502 |
| spellingShingle |
arbovirus emerging infectious diseases flavivirus serology Zika Microbiology QR1-502 Nischay Mishra Adrian Caciula Adam Price Riddhi Thakkar James Ng Lokendra V. Chauhan Komal Jain Xiaoyu Che Diego A. Espinosa Magelda Montoya Cruz Angel Balmaseda Eric H. Sullivan Jigar J. Patel Richard G. Jarman Jennifer L. Rakeman Christina T. Egan Chantal B. E. M. Reusken Marion P. G. Koopmans Eva Harris Rafal Tokarz Thomas Briese W. Ian Lipkin Diagnosis of Zika Virus Infection by Peptide Array and Enzyme-Linked Immunosorbent Assay |
| description |
ABSTRACT Zika virus (ZIKV) is implicated in fetal stillbirth, microcephaly, intracranial calcifications, and ocular anomalies following vertical transmission from infected mothers. In adults, infection may trigger autoimmune inflammatory polyneuropathy. Transmission most commonly follows the bite of infected Aedes mosquitoes but may also occur through sexual intercourse or receipt of blood products. Definitive diagnosis through detection of viral RNA is possible in serum or plasma within 10 days of disease onset, in whole blood within 3 weeks of onset, and in semen for up to 3 months. Serological diagnosis is nonetheless critical because few patients have access to molecular diagnostics during the acute phase of infection and infection may be associated with only mild or inapparent disease that does not prompt molecular testing. Serological diagnosis is confounded by cross-reactivity of immune sera with other flaviviruses endemic in the areas where ZIKV has recently emerged. Accordingly, we built a high-density microarray comprising nonredundant 12-mer peptides that tile, with one-residue overlap, the proteomes of Zika, dengue, yellow fever, West Nile, Ilheus, Oropouche, and chikungunya viruses. Serological analysis enabled discovery of a ZIKV NS2B 20-residue peptide that had high sensitivity (96.0%) and specificity (95.9%) versus natural infection with or vaccination against dengue, chikungunya, yellow fever, West Nile, tick-borne encephalitis, or Japanese encephalitis virus in a microarray assay and an enzyme-linked immunosorbent assay (ELISA) of early-convalescent-phase sera (2 to 3 weeks after onset of symptomatic infection). IMPORTANCE The emergence of Zika virus (ZIKV) as a teratogen is a profound challenge to global public health. Molecular diagnosis of infection is straightforward during the 3-week period when patients are viremic. However, serological diagnosis thereafter of historical exposure has been confounded by cross-reactivity. Using high-density peptide arrays that tile the proteomes of a selection of flaviviruses to identify a ZIKV-specific peptide, we established two assays that enable sensitive and specific diagnosis of exposure to ZIKV. These assays may be useful in guiding clinical management of mothers at risk for potential exposure to ZIKV and enable insights into the epidemiology of ZIKV infections. |
| format |
article |
| author |
Nischay Mishra Adrian Caciula Adam Price Riddhi Thakkar James Ng Lokendra V. Chauhan Komal Jain Xiaoyu Che Diego A. Espinosa Magelda Montoya Cruz Angel Balmaseda Eric H. Sullivan Jigar J. Patel Richard G. Jarman Jennifer L. Rakeman Christina T. Egan Chantal B. E. M. Reusken Marion P. G. Koopmans Eva Harris Rafal Tokarz Thomas Briese W. Ian Lipkin |
| author_facet |
Nischay Mishra Adrian Caciula Adam Price Riddhi Thakkar James Ng Lokendra V. Chauhan Komal Jain Xiaoyu Che Diego A. Espinosa Magelda Montoya Cruz Angel Balmaseda Eric H. Sullivan Jigar J. Patel Richard G. Jarman Jennifer L. Rakeman Christina T. Egan Chantal B. E. M. Reusken Marion P. G. Koopmans Eva Harris Rafal Tokarz Thomas Briese W. Ian Lipkin |
| author_sort |
Nischay Mishra |
| title |
Diagnosis of Zika Virus Infection by Peptide Array and Enzyme-Linked Immunosorbent Assay |
| title_short |
Diagnosis of Zika Virus Infection by Peptide Array and Enzyme-Linked Immunosorbent Assay |
| title_full |
Diagnosis of Zika Virus Infection by Peptide Array and Enzyme-Linked Immunosorbent Assay |
| title_fullStr |
Diagnosis of Zika Virus Infection by Peptide Array and Enzyme-Linked Immunosorbent Assay |
| title_full_unstemmed |
Diagnosis of Zika Virus Infection by Peptide Array and Enzyme-Linked Immunosorbent Assay |
| title_sort |
diagnosis of zika virus infection by peptide array and enzyme-linked immunosorbent assay |
| publisher |
American Society for Microbiology |
| publishDate |
2018 |
| url |
https://doaj.org/article/b09d562b006747a79f5be39b615d3603 |
| work_keys_str_mv |
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