Strain-dependent activity of Zika virus and exposure history in serological diagnostics

• Published in: Tropical medicine and infectious disease Vol. 5; no. 1; pp. 1 - 14
• Main Authors: Barr, Kelli L., Schwarz, Erika R., Prakoso, Dhani, Imtiaz, Kehkashan, Pu, Ruiyu, Morris, J. Glenn, Khan, Erum, Long, Maureen T.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2020; MDPI
• Subjects: Antibodies; cross-reactivity; Diagnosis; diagnostics; flavivirus; flavivirus exposure; Flaviviruses; Genetic aspects; Health aspects; neutralization; Physiological aspects; plaque reduction neutralization test; Risk factors; Serodiagnosis; Serology; Technique; Zika virus; Zika virus infection; Pakistan; diagnostics; neutralization; flavivirus exposure; serology; plaque reduction neutralization test; Zika virus; cross-reactivity; flavivirus
• ISSN: 2414-6366; 2414-6366
• DOI: 10.3390/tropicalmed5010038

Zika virus (ZIKV) circulates as two separate lineages, with significant genetic variability between strains. Strain-dependent activity has been reported for dengue virus, herpes simplex virus and influenza. Strain-dependent activity of subject specimens to a virus could be an impediment to serological diagnosis and vaccine development. In order to determine whether ZIKV exhibits strain-dependent activity when exposed to antibodies, we measured the neutralizing properties of polyclonal serum and three monoclonal antibodies (ZKA185, 753(3)C10, and 4G2) against three strains of ZIKV (MR-766, PRVABC59, and R103454). Here, MR-766 was inhibited almost 60% less by ZKA185 than PRVABC59 and R103454 (p = 0.008). ZKA185 enhanced dengue 4 infection up to 50% (p = 0.0058). PRVABC59 was not inhibited by mAb 753(3)C10 while MR-766 and R103453 were inhibited up to 90% (p = 0.04 and 0.036, respectively). Patient serum, regardless of exposure history, neutralized MR-766 30%-40% better than PRVABC56 or R103454 (p = 0.005-0.00007). The most troubling finding was the significant neutralization of MR-766 by patients with no ZIKV exposure. We also evaluated ZIKV antibody cross reactivity with various flaviviruses and found that more patients developed cross-reactive antibodies to Japanese encephalitis virus than the dengue viruses. The data here show that serological diagnosis of ZIKV is complicated and that qualitative neutralization assays cannot discriminate between flaviviruses.