ABSTRACT
Zika virus (ZIKV) infections have gained notoriety due to congenital abnormalities. Pregnant women have a greater risk of ZIKV infection and consequent transmission to their progeny due to the immunological changes associated with pregnancy. ZIKV has been detected in amniotic fluid, as well as in fetal and neonatal tissues of infected pregnant women. However, the mechanism by which ZIKV reaches the fetus is not well understood. The four dengue virus serotypes have been the most widely used flaviviruses to elucidate the host-cell entry pathways. Nevertheless, it is of increasing interest to understand the specific interaction between ZIKV and the host cell, especially in the gestation period. Herein, the authors describe the mechanisms of prenatal vertical infection of ZIKV based on results from in vitro, in vivo, and ex vivo studies, including murine models and nonhuman primates. It also includes up-to-date knowledge from ex vivo and natural infections in pregnant women explaining the vertical transmission along four tracks: transplacental, paracellular, transcytosis mediated by extracellular vesicles, and paraplacental route and the antibody-dependent enhancement process. A global understanding of the diverse pathways used by ZIKV to cross the placental barrier and access the fetus, along with a better comprehension of the pathogenesis of ZIKV in pregnant females, may constitute a fundamental role in the design of antiviral drugs to reduce congenital disabilities associated with ZIKV.
Subject(s)
Pregnancy Complications, Infectious , Zika Virus Infection , Zika Virus , Animals , Female , Humans , Infectious Disease Transmission, Vertical , Mice , Placenta , PregnancyABSTRACT
Virus-like particles are excellent inducers of the adaptive immune response of humans and are presently being used as scaffolds for the presentation of foreign peptides and antigens derived from infectious microorganisms for subunit vaccine development. The most common approaches for peptide and antigen presentation are translational fusions and chemical coupling, but some alternatives that seek to simplify the coupling process have been reported recently. In this work, an alternative platform for coupling full antigens to virus-like particles is presented. Heterodimerization motifs inserted in both Tobacco etch virus coat protein and green fluorescent protein directed the coupling process by simple mixing, and the obtained complexes were easily taken up by a macrophage cell line.
Subject(s)
Antigen Presentation/immunology , Antigens , Potyvirus , Vaccines, Virus-Like Particle , Animals , Antigens/chemistry , Antigens/immunology , Mice , Potyvirus/chemistry , Potyvirus/immunology , RAW 264.7 Cells , Vaccines, Virus-Like Particle/chemistry , Vaccines, Virus-Like Particle/immunologyABSTRACT
Porcine reproductive and respiratory syndrome virus (PRRSV) still poses a threat to the swine industry worldwide. Currently, commercial vaccines against PRRSV, which consist of modified live or inactivated virus, reduce symptoms and viremia in immunized pigs, but efficacy against heterologous strains is variable. This has led to the development of subunit vaccines that contain viral antigens that show the highest variability. In this work, a chimeric protein comprising short amino acid sequences from glycoprotein 3 (GP3), glycoprotein 4 (GP4), glycoprotein 5 (GP5), and M (matrix protein) proteins of PRRSV was designed and expressed in Escherichia coli. This protein, designated as PRRSVchim, was purified by immobilized metal affinity chromatography and evaluated. PRRSVchim was identified by immunoglobulin G (IgG) presence in serum samples from PRRSV-positive pigs. Also, the protein probed to be antigenic in immunized mice and piglets and provided some degree of protection against challenge with a PRRSV field isolate. These results show the potential of PRRSVchim protein for both PRRSV diagnostic and immunoprophylaxis.
