Enhancement Of Zika Virus Infection By West Nile And Dengue Virus Antibody Positive Cord-Blood Samples From Mothers In El Paso-Texas

The recent Zika virus (ZIKV) outbreak and its association with microcephaly cases and other neurological syndromes are important public health concerns. A phenomenon known as antibody-dependent enhancement (ADE) involves preexisting flavivirus antibodies to a specific flavivirus that enhances the severity of a second infection with a different flavivirus. Since ZIKV is related to flaviviruses like West Nile virus (WNV) and dengue virus (DENV), prior exposure to these viruses could elicit cross-reactive antibodies that may enhance a subsequent ZIKV infection. Therefore, this study aimed to determine if WNV and DENV antibodies from cord blood enhanced ZIKV infection in vitro. Initially, a serosurvey was conducted to determine the prevalence rate of DENV, WNV, and other flavivirus antibodies by screening of 910 human umbilical cord blood samples collected between 2016 and 2017 in El Paso, Texas. The samples were tested for IgG antibody with an enzyme-linked immunosorbent assay (ELISA), and for neutralizing antibodies, plaque-reduction neutralization tests (PRNT80) to confirm the virus-specific antibodies. The seroprevalence for DENV, WNV, and SLEV was 1.97% (18/910), 4.39% (40/910), and 0.11 % (1/910) respectively. From this study, flavivirus cord blood seropositive samples for DENV (n= 17), WNV (n=39 and SLEV (n=1), were selected to determine the possibility of neutralization and/or enhancement of ZIKV infection by WNV, DENV and SLEV antibodies using reporter virus particles (RVPs). Also, the same method was used to determine if DENV-1 infection was enhanced and/or neutralized by WNV, DENV, and SLEV antibodies. The results revealed that ZIKV and DENV-1 infections were neutralized by WNV and DENV-1 antibodies at dilutions that reduced 80% of the viral plaque forming units, but on diluting the samples beyond the neutralization endpoint, the WNV and DENV-1 antibodies enhanced at dilution of 1:40 by DENV, WNV and SLEV antibodies. Moreover, ZIKV and DENV-1 infection was enhanced from 1:40 to 1:640, and from 1:160 to 1:10240 by DENV antibody respectively. Our findings supported previous findings of ongoing transmission of WNV in the El Paso community but did not provide conclusive evidence that DENV was endemic in the El Paso community. Furthermore, our results suggested that if ZIKV was introduced into the El Paso community, infection by this virus would be enhanced by these flavivirus antibodies to produce more severe disease. Further studies are warranted to determine if pre-existing WNV and DENV antibodies diluted at 1:40 enhance ZIKV infection in vivo. Finally, this is the first study that described the possible ADE to ZIKV and DENV infection in blood cord samples from a U.S. border community and contributed to its understanding.