Preprint Article Version 1 This version is not peer-reviewed

Cross-Reactivity of Zika and Other Flaviviruses in Serological Diagnostics

Version 1 : Received: 25 November 2019 / Approved: 27 November 2019 / Online: 27 November 2019 (03:45:37 CET)

How to cite: Barr, K.L.; Schwarz, E.R.; Prakoso, D.; Imtiaz, K.; Pu, R.; Morris Jr., J.G.; Khan, E.; Long, M.T. Cross-Reactivity of Zika and Other Flaviviruses in Serological Diagnostics. Preprints 2019, 2019110323 (doi: 10.20944/preprints201911.0323.v1). Barr, K.L.; Schwarz, E.R.; Prakoso, D.; Imtiaz, K.; Pu, R.; Morris Jr., J.G.; Khan, E.; Long, M.T. Cross-Reactivity of Zika and Other Flaviviruses in Serological Diagnostics. Preprints 2019, 2019110323 (doi: 10.20944/preprints201911.0323.v1).

Abstract

Zika virus (ZIKV) co-circulates with several closely related flaviviruses which exhibit similar clinical manifestations thus, clinicians rely on molecular and serological techniques for diagnosis. Cross-reactivity of patient specimens to flaviviruses is a significant impediment to serological diagnosis in areas where multiple flaviviruses co-circulate. Furthermore, patient exposure history to any of these viruses could complicate serological response patterns which could result in over and/or underdiagnosis of ZIKV infection. Three strains of ZIKV, dengue serotypes 1-4, West Nile virus, Japanese Encephalitis virus, and Yellow Fever virus were evaluated for neutralizing properties against 3 monoclonal antibodies, 4 ZIKV-naïve patients with flavivirus exposure history, 5 patients with verified ZIKV exposure and unknown flavivirus exposure history, and 5 flavivirus-naive patients with ZIKV-only exposure. Patients naïve for ZIKV exposure effectively neutralized multiple strains of ZIKV. Overall, the prototype ZIKV isolate MR-766 did not behave like the other ZIKV isolated used in this study. MR-766 was neutralized more completely by polyclonal patient serum than recent ZIKV isolates. MR-766 was neutralized better than dengue virus in ZIKV-naïve patients with prior dengue exposure. MR-766 was neutralized significantly less than recent ZIKV isolates when treated with monoclonal antibodies. The data herein show that without RT-PCR, serological diagnosis may not be possible in areas where multiple flaviviruses are endemic.

Subject Areas

Zika virus; flavivirus; cross-reactivity; neutralization; diagnostics; serology; plaque reduction neutralization test; flavivirus exposure

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