Abstract
Dengue virus (DENV) and Zika virus (ZIKV) are two mosquito-borne flaviviruses afflicting nearly half of the world population. Human infection by these viruses can either be asymptomatic or manifest as clinical diseases from mild to severe. Despite more cases are presented as self-limiting febrile illness, severe dengue disease can be manifested as hemorrhagic fever and hemorrhagic shock syndrome, and ZIKV infection has been linked to increased incidence of peripheral neuropathy Guillain-Barre syndrome and central neural disease such as microcephaly. The current prevention and treatment of these infectious diseases are either non-satisfactory or entirely lacking. Because DENV and ZIKV have much similarities in genomic and structural features, almost identical mode of mosquito-mediated transmission, and probably the same pattern of host innate and adaptive immunity toward them, it is reasonable and often desirable to investigate these two viruses side-by-side, and thereby devise common countermeasures against both. Here, we review the existing knowledge on DENV and ZIKV regarding epidemiology, molecular virology, protective immunity and vaccine development, discuss recent new discoveries on the functions of flavivirus NS1 protein in viral pathogenesis and transmission, and propose a one-two punch strategy using vaccine and vector blockade to overcome antibody-dependent enhancement and defeat Dengue and Zika viruses.
Highlights
Reviewed by: Cheng-Feng Qin, Beijing Institute of Microbiology and Epidemiology, China Svetlana Khaiboullina, University of Nevada, Reno, United States Jing An, Capital Medical University, China
Despite more cases are presented as self-limiting febrile illness, severe dengue disease can be manifested as hemorrhagic fever and hemorrhagic shock syndrome, and Zika virus (ZIKV) infection has been linked to increased incidence of peripheral neuropathy Guillain-Barre syndrome and central neural disease such as microcephaly
Our studies have demonstrated that monocyte was the principle target cell among PBMCs for both Dengue virus (DENV) and ZIKV infection, as well as the main mediators for Antibody Dependent Enhancement (ADE) of both viruses in PBMCs (Kou et al, 2008; Li et al, 2018)
Summary
Based on the existing knowledge of vaccine immunology and protective immunity to DENV and ZIKV, it is predicted that an ideal dengue or Zika vaccine should induce both humoral and cellular immune response to ensure full protection. Much evidence indicated NS1 antibodies being capable of cross-react with coagulation factors and adhesin molecules on platelets and endothelial cells, causing disruption of platelet aggregation and apoptosis of endothelial cells, and leading to pathology in DENV infections (Falconar, 1997; Lin et al, 2005; Cheng et al, 2009; Liu et al, 2011) Based on these evidence, we had constructed a modified DENV2 sNS1 with deletion of epitopes mimicking autoantigens ( NS1), and found that prior immunization with either NS1 or full-length NS1 in AG6 mice significantly helped to neutralize NS1 antigenemia and block the transmission of virus to mosquitoes. Though further investigations are necessary, this might imply the importance of CD4 + T cell immunity in blocking sexual transmission, which should be considered during vaccine design (Elong Ngono et al, 2019)
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