Because dengue virus serotypes (DENV1-4) and Zika virus (ZIKV) are related flaviviruses, and monoclonal antibodies and plasma from DENV-immune donors can neutralise or enhance ZIKV in vitro and in small-animal models and vice versa, the authors were interested in the extent, duration and significance of this cross-reactivity in humans. They examined the neutralising antibodies to ZIKV and DENV1-4 in longitudinal serologic samples collected up to 3 years following infection from people in Latin America and Asia with laboratory-confirmed DENV infections. They also assessed the neutralising antibodies to ZIKV and DENV1-4 in patients with Zika up to 6 months following infection. The authors found that in patients with Zika virus infection, the highest neutralising antibody titres were to ZIKV, with low-level cross-reactivity to DENV1-4 that was greater in DENV-immune patients. The authors also found that, in primary and secondary DENV infections, neutralising antibody titres to ZIKV were markedly lower than to the infecting DENV and heterologous DENV serotypes. Cross-neutralisation was greatest in early convalescence, then ZIKV neutralisation decreased to low levels over time. Therefore it is likely that ZIKV lies outside of the DENV serocomplex. Neutralising antibody titres can therefore be used to distinguish ZIKV from DENV infections when all viruses are analysed simultaneously.
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