title: Preventive and therapeutic challenges in combating Zika virus infection: are we getting any closer?
abstract: The neuroteratogenic nature of Zika Virus (ZIKV) infection has converted what would have been a tropical disease into a global threat. Zika is transmitted vertically via infected placental cells especially in the first and second trimesters. In the developing central nervous system (CNS), ZIKV can infect and induce apoptosis of neural progenitor cells subsequently causing microcephaly as well as other neuronal complications in infants. Its ability to infect multiple cell types (placental, dermal, and neural) and increased environmental stability as compared to other flaviviruses (FVs) has broadened the transmission routes for ZIKV infection from vector-mediated to transmitted via body fluids. To further complicate the matters, it is genetically similar (about 40%) with the four serotypes of dengue virus (DENV), so much so that it can almost be called a fifth DENV serotype. This homology poses the risk of causing cross-reactive immune responses and subsequent antibody-dependent enhancement (ADE) of infection in case of secondary infections or for immunized individuals. All of these factors complicate the development of a single preventive vaccine candidate or a pharmacological intervention that will completely eliminate or cure ZIKV infection. We discuss all of these factors in detail in this review and conclude that a combinatorial approach including immunization and treatment might prove to be the winning strategy.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY, 14642, USA. meera_singh@urmc.rochester.edu.
authors.forename: Meera V
authors.initials: MV
authors.lastname: Singh
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY, 14642, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Weber
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY, 14642, USA.
authors.forename: Vir B
authors.initials: VB
authors.lastname: Singh
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY, 14642, USA.
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Stirpe
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY, 14642, USA.
authors.forename: Sanjay B
authors.initials: SB
authors.lastname: Maggirwar
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D001430:Bacteriocins / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003514:Cyclohexylamines / Q000627:therapeutic use; D003716:Dengue Virus / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D005260:Female; D005333:Fetus; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008831:Microcephaly / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D010455:Peptides / Q000627:therapeutic use; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D019595:Severe Dengue / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission / Q000821:virology; D013876:Thiophenes / Q000627:therapeutic use; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000096:biosynthesis; D000071244:Zika Virus / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology; D000071243:Zika Virus Infection / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission / Q000821:virology
chemical_list: D000998:Antiviral Agents; D001430:Bacteriocins; D003514:Cyclohexylamines; D010455:Peptides; C468918:SAG compound; D013876:Thiophenes; D014765:Viral Vaccines; C040522:duramycin
keywords: Antibody dependent enhancement of infection; Microcephaly; Therapeutics; Zika virus