Overview on the Current Status of Zika Virus Pathogenesis and Animal Related Research

Abstract

There is growing evidence that Zika virus (ZIKV) infection is linked with activation of Guillan-Barré syndrome (GBS) in adults infected with the virus and microcephaly in infants following maternal infection. With the recent outpour in publications by numerous research labs, the association between microcephaly in newborns and ZIKV has become very apparent in which large numbers of viral particles were found in the central nervous tissue of an electively aborted microcephalic ZIKV-infected fetus. However, the underlying related mechanisms remain poorly understood. Thus, development of ZIKV-infected animal models are urgently required. The need to develop drugs and vaccines of high efficacy along with efficient diagnostic tools for ZIKV treatment and management raised the demand for a very selective animal model for exploring ZIKV pathogenesis and related mechanisms. In this review, we describe recent advances in animal models developed for studying ZIKV pathogenesis and evaluating potential interventions against human infection, including during pregnancy. The current research directions and the scientific challenges ahead in developing effective vaccines and therapeutics are also discussed.

ICR suckling mouse model of Zika virus infection for disease modeling and drug validation

“…There observations in ICR suckling mice may provide the phenomenon for investigation of the efficacy of developing drug or vaccine, and the tissue of the suckling mice may use to underlying the mechanism discovery [ 20 ]. However, the limitation of AG129 mice is unable to develop the vaccine or drug that is dependent on the intact interferon pathway [ 33 ]. Furthermore, AG129 and Irf3/5/7 TKO mice has been indicated to be uncommonly available in some research laboratories [ 33 , 34 ].…”

“…However, the limitation of AG129 mice is unable to develop the vaccine or drug that is dependent on the intact interferon pathway [ 33 ]. Furthermore, AG129 and Irf3/5/7 TKO mice has been indicated to be uncommonly available in some research laboratories [ 33 , 34 ]. The ICR suckling mice model are the immunocompetent mice, which have allowed researchers to investigate the interferon-dependent antiviral compounds or vaccine [ 20 , 35 ].…”

Complementary Mechanisms Potentially Involved in the Pathology of Zika Virus

“…So far several animal models have been proposed for ZIKV infection, including immunocompetent mice (C57BL/6), mice lacking the receptors for interferon (IFNAR), mice neutralized with the IFNAR antibodies, mice lacking IRF3/5/7, immunocompetent non-human primates and chicken embryos [Reviewed in ( 101 ) and ( 102 )]. The most commonly employed mice models are the A129 strain which lacks the receptors for type 1 interferon and the AG129 strain which lacks the receptors for both type 1 and 2 IFN ( 27 , 103 , 104 ).…”

“…Comparable results can be achieved when using C57BL/6 mice treated with IFNAR1 monoclonal antibody prior to and during viral infection or using Irf3 −/− Irf5 −/− Irf7 −/− triple knockout mice ( 27 , 103 ). Despite many advances in using ZIKV-infected mouse model in establishing the cell tropism, viral replication kinetics, host immune response, teratogenicity, and clinical manifestation, limited progress toward vaccine development has been made ( 53 , 102 ). Structural and immunological dissimilarities between human and mice placenta, resistance of immunocompetent mice to ZIKV replication, skepticism about the relevance of data generated from immune compromised or genetically modified mice, limited availability of non-human primates and associated high cost are some of the limitations that are currently manifesting with the use of animal models ( 101 ).…”

Zika Virus: Mode of transmission, Outrageous Effects and Clinical Trials

“…Zika virus complications can find the association with guillian barre syndrome (GBS) and it was confirmed by magnetic resonance imaging. GBS is an autoimmune neuropathy which attacks peripheral nervous system that leads to muscle weakness, numbness, paralysis and might be death [15]. In the outbreak of French Polynesia in 2013-2014, 38 cases of ZIKV disease were established to have the Guillain-Barré syndrome.…”