Zika Virus Pathogenesis: A Battle for Immune Evasion

Abstract

Zika virus (ZIKV) infection and its associated congenital and other neurological disorders, particularly microcephaly and other fetal developmental abnormalities, constitute a World Health Organization (WHO) Zika Virus Research Agenda within the WHO’s R&D Blueprint for Action to Prevent Epidemics, and continue to be a Public Health Emergency of International Concern (PHEIC) today. ZIKV pathogenicity is initiated by viral infection and propagation across multiple placental and fetal tissue barriers, and is critically strengthened by subverting host immunity. ZIKV immune evasion involves viral non-structural proteins, genomic and non-coding RNA and microRNA (miRNA) to modulate interferon (IFN) signaling and production, interfering with intracellular signal pathways and autophagy, and promoting cellular environment changes together with secretion of cellular components to escape innate and adaptive immunity and further infect privileged immune organs/tissues such as the placenta and eyes. This review includes a description of recent advances in the understanding of the mechanisms underlying ZIKV immune modulation and evasion that strongly condition viral pathogenesis, which would certainly contribute to the development of anti-ZIKV strategies, drugs, and vaccines.

Pathophysiological and molecular considerations of viral and bacterial infections during maternal-fetal and –neonatal interactions of SARS-CoV-2, Zika, and Mycoplasma infectious diseases

“…ZIKV invades the villi without infecting the syncytiotrophoblast and thus the virus does not cross the placental barrier [ 37 ]. This is enough for immune evasion of ZIKV [ 95 ], resulting in a key role of the infection of the maternal residual tissues to explain the pathogenesis of ZIKV infection in the maternal-fetal interface, with its consequences in the embryo and fetus [ 96 ]. ZIKV replicates in proliferating explants from first-trimester human placentas, being these cells possible locations for the propagation of the infection [ 97 ].…”

Are the Organoid Models an Invaluable Contribution to ZIKA Virus Research?

“…In these latter, large numbers of macrophages are recruited and amplify the virus spreads to monocytes, macrophages or dendritic cells in multiple tissues reaching the remaining tissues. In fact, in rhesus macaques, in situ hybridizations have demonstrated that neurons, macrophages, neutrophils, and dendritic cells are permissive [21][22][23]. Not only it can persist in the macaque central nervous system but also in the lymphoid tissue for over 4 weeks after infections [23,24].…”

Systemic inflammation, innate immunity and pathogenesis after Zika virus infection in cynomolgus macaques are modulated by strain-specificity within the Asian lineage

“…Although ZIKV is rarely associated with mortality or severe acute disease, based on epidemiological data ZIKV infections have also been linked with rare neurological diseases and autoimmune Guillain-Barré Syndrome (GBS) [5,6,11,12].…”

“…Although ZIKV is primarily spread through the Aedes mosquito vector, other means of transmission have also been reported [ 3 , 4 ]. Maternal-to-fetal vertical transmission of ZIKV through the placenta during pregnancy have been linked with increased risk of preterm birth, stillbirth, as well as a number of debilitating neurological congenital pathologies collectively grouped under the term congenital Zika syndrome (CZS) (which includes microcephaly, abnormal development of the brain, ocular pathologies, limb contractures and other neurologic abnormalities) [ 5–7 , 8 ]. Conversely, acute ZIKV infection in adults often remains unnoticed, and symptomatic cases are characterized by a mild flu-like disease, inluding fever, headaches, myalgia and arthralgia, and occasionally conjuncivitis, rash, and gastro-intestinal signs, with an onset at 3–12 days after exposure [ 9 , 10 ].…”

“…Conversely, acute ZIKV infection in adults often remains unnoticed, and symptomatic cases are characterized by a mild flu-like disease, inluding fever, headaches, myalgia and arthralgia, and occasionally conjuncivitis, rash, and gastro-intestinal signs, with an onset at 3–12 days after exposure [ 9 , 10 ]. Although ZIKV is rarely associated with mortality or severe acute disease, based on epidemiological data ZIKV infections have also been linked with rare neurological diseases and autoimmune Guillain-Barré Syndrome (GBS) [ 5 , 6 , 11 , 12 ].…”