Humoral response against Zika virus infection is dependent on type I interferon pathway
Cheryl Yi-Pin Lee1,2, Lisa F.P. Ng 1,3,4
1Singapore Immunology Network, Agency for Technology and Research (A*STAR), Biopolis, Singapore; 2NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore; 3Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 4Institute of Infection and Global Health, University of Liverpool, UK
Zika virus (ZIKV) is an arthropod-borne virus that has presented as a global threat, especially with substantial evidence that associates ZIKV with neurological implications, including Guillain-Barré syndrome and congenital ZIKV syndrome. Previously, we demonstrated that ZIKV-infected adult IFNAR-/- mice presented clinical symptoms of hunchback and hind limb paralysis, and eventually succumbed to the infection. Notably, ZIKV infection done in pregnant IFNAR-/- animals led to significant congenital development anomalies with high levels of viral RNA detected in fetal organs including fetal brain. These findings further exemplified the importance of type I interferon (IFN) response during ZIKV infection. The administration of cross-reactive Dengue virus (DENV) monoclonal antibodies (mAbs) to ZIKV-infected adult and pregnant IFNAR-/- mice rescued the phenotypes and prevented mortality. Apart from using DENV-specific mAbs, it is also essential to develop mAbs that are specific to ZIKV. As such, subsequent efforts were made to identify potential ZIKV-specific antibodies that display protective properties. Since immunocompetent WT mice were poorly susceptible to ZIKV infection due to a robust innate immune response, antibody production from these animals were negligible. Hence, blockade of type I IFN pathway in these WT mice was done to induce persisting viremia, which could prime an active humoral response. Interestingly, antibody profiling on serum from both WT and type I IFN-suppressed WT (WTIFN) mice showed a difference in antibody quantity and quality. Although WTIFN animals have lower ZIKV-specific antibody production, these antibodies were more neutralising against ZIKV infection. Taken together, our data highlight the importance of type I IFN response as both a deterrent against viral infection, and a key regulator of humoral immune response during ZIKV infection.