Modulation of Dengue/Zika Virus Pathogenicity by Antibody-Dependent Enhancement and Strategies to Protect Against Enhancement in Zika Virus Infection.

摘要: Antibody-dependent enhancement (ADE) is a phenomenon in which preexisting poorly neutralizing antibodies leads to enhanced infection. It serious concern with mosquito-borne flaviviruses such as Dengue virus (DENV) and Zika (ZIKV). In vitro experimental evidences have indicated the preventive, well pathogenicity-enhancing role, of DENV ZIKV infections. ADE has been confirmed but not Principally, Fc region anti-DENV antibody binds fragment crystallizable gamma receptor (FcγR), subsequent C1q interactions immune effector functions are responsible for ADE. contrast normal infections, inhibition STAT1 phosphorylation reduction IRF-1 gene expression, NOS2 levels, RIG-1 MDA-5 expression levels occurs. FcγRIIA most permissive FcγR DENV-ADE, under hypoxic conditions, hypoxia-inducible factor-1 alpha transcriptionally enhances FcγRIIA, further To produce therapeutic broad reactivity different serotypes, ZIKV, bispecific antibodies, mutants, modified regions, anti-idiotypic may be engineered. An in-depth understanding immunological molecular mechanisms DENV-ADE pathogenicity will useful design common safe therapeutics prophylactics against both viral pathogens. The present review discusses role modulating DENV/ZIKV pathogenicity/infection strategies counter protect