Although transmission of Zika virus (ZIKV) in the Americas has greatly declined since late 2017, recent reports of reduced risks of symptomatic Zika by prior dengue virus (DENV)
infection and increased risks of
severe dengue disease by previous ZIKV or DENV
infection underscore a critical need for serological tests that can discriminate past ZIKV, DENV, and/or other
flavivirus infections and improve our understanding of the immune interactions between these viruses and
vaccine strategy in endemic regions. As serological tests for ZIKV primarily focus on envelope (E) and nonstructural
protein 1 (NS1),
antibodies to other ZIKV
proteins have not been explored. Here, we employed Western blot analysis using
antigens of 6 flaviviruses from 3 serocomplexes to investigate antibody responses following reverse transcription-PCR (RT-PCR)-confirmed
ZIKV infection. Panels of 20 primary ZIKV and 20 ZIKV with previous DENV
infection recognized E
proteins of all 6 flaviviruses and the NS1
protein of ZIKV with some cross-reactivity to DENV. While the primary ZIKV panel recognized only the premembrane (prM)
protein of ZIKV, the ZIKV with previous DENV panel recognized both ZIKV and DENV prM
proteins. Analysis of antibody responses following 42 DENV and 18 West Nile virus
infections revealed similar patterns of recognition by anti-E and anti-NS1
antibodies, whereas both panels recognized the prM
protein of the homologous serocomplex but not others. The specificity was further supported by analysis of sequential samples. Together, these findings suggest that anti-prM antibody is a flavivirus serocomplex-specific marker and can be used to delineate current and past
flavivirus infections in endemic areas. IMPORTANCE Despite a decline in Zika virus (ZIKV) transmission since late 2017, questions regarding its surveillance, potential reemergence, and interactions with other flaviviruses in regions where it is endemic remain unanswered. Recent studies have reported reduced risks of symptomatic Zika by prior dengue virus (DENV)
infection and increased risks of
severe dengue disease by previous ZIKV or DENV
infection, highlighting a need for better serological tests to discriminate past ZIKV, DENV, and/or other
flavivirus infections and improved understanding of the immune interactions and
vaccine strategy for these viruses. As most serological tests for ZIKV focused on envelope and nonstructural
protein 1,
antibodies to other ZIKV
proteins, including potentially specific
antibodies, remain understudied. We employed Western blot analysis using
antigens of 6 flaviviruses to study antibody responses following well-documented ZIKV, DENV, and West Nile virus
infections and identified anti-premembrane antibody as a flavivirus serocomplex-specific marker to delineate current and past
flavivirus infections in areas where flaviviruses are endemic.