Dengue Virus Immunopathogenesis: Lessons Applicable to the Emergence of Zika Virus

Olagnier, David; Amatore, Donatella; Castiello, Luciano; Ferrari, Matteo; Palermo, Enrico; Diamond, Michael S.; Palamara, Anna Teresa; Hiscott, John

doi:10.1016/j.jmb.2016.04.024

Cited by 39 publications

(33 citation statements)

References 177 publications

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“…For the current outbreak in the Americas and the Caribbean, this is of major public health concern. It is not clear how preexisting antibody titers to other flaviviruses might affect the quality of immune responses generated to ZIKV infection and, equally important, whether such cross-reactive antibodies provide protective immunity or impact disease severity in infected adults (18). In the study presented here, we have determined the degree by which dengue-induced antibodies cross-react with ZIKV, both at a serum level as well as at a singlecell level.…”

Section: Discussionmentioning

confidence: 99%

Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus

Priyamvada

Quicke

Hudson

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

509

482

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Zika virus (ZIKV) is an emerging mosquito-borne flavivirus of significant public health concern. ZIKV shares a high degree of sequence and structural homology compared with other flaviviruses, including dengue virus (DENV), resulting in immunological cross-reactivity. Improving our current understanding of the extent and characteristics of this immunological cross-reactivity is important, as ZIKV is presently circulating in areas that are highly endemic for dengue. To assess the magnitude and functional quality of cross-reactive immune responses between these closely related viruses, we tested acute and convalescent sera from nine Thai patients with PCRconfirmed DENV infection against ZIKV. All of the sera tested were cross-reactive with ZIKV, both in binding and in neutralization. To deconstruct the observed serum cross-reactivity in depth, we also characterized a panel of DENV-specific plasmablast-derived monoclonal antibodies (mAbs) for activity against ZIKV. Nearly half of the 47 DENV-reactive mAbs studied bound to both whole ZIKV virion and ZIKV lysate, of which a subset also neutralized ZIKV. In addition, both sera and mAbs from the dengue-infected patients enhanced ZIKV infection of Fc gamma receptor (FcγR)-bearing cells in vitro. Taken together, these findings suggest that preexisting immunity to DENV may impact protective immune responses against ZIKV. In addition, the extensive cross-reactivity may have implications for ZIKV virulence and disease severity in DENV-experienced populations. (2-4). However, the more recent outbreaks have caused severe neurological complications including GuillainBarré Syndrome in adults and an increase in congenital microcephaly and other adverse birth outcomes in Brazil (5-7). The Pan American Health Organization has reported that as of May 2016, local transmission of ZIKV had spread to over 38 countries or territories in the Americas. In addition, a recent WHO report states that 44 new countries are experiencing their first ZIKV outbreak since 2015. Despite the improving surveillance of the virus, accurate diagnosis has been challenging given the similarities in the clinical presentation of ZIKV to other arboviral infections endemic in these regions, among other factors.During the viremic period, ZIKV can be found in patient blood, saliva, urine, and other bodily fluids early after symptom onset (8-10). During the Yap Islands epidemic in 2007, anti-ZIKV IgM ELISAs and ZIKV plaque reduction neutralization titer (PRNT) assays were performed to confirm infection in RT-PCR negative cases (2, 8). However, as these studies showed, the cross-reactivity between ZIKV and other flaviviruses makes confirmation of infection difficult, especially when patients may have had flavivirus exposures before their suspected ZIKV infection (2,8). Given the overlapping presence of DENV and other flaviviruses in a majority of ZIKV epidemic regions (11), there are great challenges in serology-based testing of flavivirus-immune patients (12).The DENV envelope (E) protein, considered a major imun...

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Section: Discussionmentioning

confidence: 99%

Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus

Priyamvada

Quicke

Hudson

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

509

482

View full text Add to dashboard Cite

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“…1). The non-structural proteins are important for entry, translation, replication, morphogenesis, and pathogenesis (Lindenbach and Rice, 2003; Olagnier et al, 2016; Sirohi et al, 2016). The ORF is flanked by highly conserved secondary structures at the 5′ and 3′ untranslated regions that help in translation and replication of the genome (Zhu et al, 2016).…”

Section: Zika Virus Genome Organization and Polyprotein Processingmentioning

confidence: 99%

Host-Virus Interaction of ZIKA Virus in Modulating Disease Pathogenesis

Routhu

Byrareddy

2017

J Neuroimmune Pharmacol

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The Zika virus (ZIKV) is a newly emerging pathogen that has resulted in a worldwide epidemic. It primarily spreads either through infected Aedes aegypti or Aedes albopictus mosquitos leading to severe neurological disorders such as microcephaly and Guillain-Barré syndrome in susceptible individuals. The mode of ZIKV entry into specific cell types such as: epidermal keratinocytes, fibroblasts, immature dendritic cells (iDCs), and stem-cell-derived human neural progenitors has been determined through its major surface envelope glycoprotein. It has been known that oligosaccharides that are covalently linked to viral envelope proteins are crucial in defining host-virus interactions. However, the role of sugars/glycans in exploiting host-immune mechanisms and aiding receptor-mediated virus entry is not well defined. Therefore, this review focuses on host-pathogen-interactions to better understand ZIKV pathogenesis.

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“…Mosquito-borne FVs primarily cause acute febrile infections that are transient and resolve in ~2 weeks (19–21). Approximately 80% of FV infections are asymptomatic, with neurologic symptoms in <1% of Japanese encephalitis virus (JEV) and West Nile virus (WNV) cases and in an even smaller subset of dengue virus (DENV)-infected individuals.…”

Section: Introductionmentioning

confidence: 99%

Zika Virus Persistently Infects and Is Basolaterally Released from Primary Human Brain Microvascular Endothelial Cells

Mladinich

Schwedes

Mackow

2017

mBio

110

150

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Zika virus (ZIKV) is a mosquito-borne Flavivirus that has emerged as the cause of encephalitis and fetal microencephaly in the Americas. ZIKV uniquely persists in human bodily fluids for up to 6 months, is sexually transmitted, and traverses the placenta and the blood-brain barrier (BBB) to damage neurons. Cells that support persistent ZIKV replication and mechanisms by which ZIKV establishes persistence remain enigmatic but central to ZIKV entry into protected neuronal compartments. The endothelial cell (EC) lining of capillaries normally constrains transplacental transmission and forms the BBB, which selectively restricts access of blood constituents to neurons. We found that ZIKV (strain PRVABC59) persistently infects and continuously replicates in primary human brain microvascular ECs (hBMECs), without cytopathology, for >9 days and following hBMEC passage. ZIKV did not permeabilize hBMECs but was released basolaterally from polarized hBMECs, suggesting a direct mechanism for ZIKV to cross the BBB. ZIKV-infected hBMECs were rapidly resistant to alpha interferon (IFN-α) and transiently induced, but failed to secrete, IFN-β and IFN-λ. Global transcriptome analysis determined that ZIKV constitutively induced IFN regulatory factor 7 (IRF7), IRF9, and IFN-stimulated genes (ISGs) 1 to 9 days postinfection, despite persistently replicating in hBMECs. ZIKV constitutively induced ISG15, HERC5, and USP18, which are linked to hepatitis C virus (HCV) persistence and IFN regulation, chemokine CCL5, which is associated with immunopathogenesis, as well as cell survival factors. Our results reveal that hBMECs act as a reservoir of persistent ZIKV replication, suggest routes for ZIKV to cross hBMECs into neuronal compartments, and define novel mechanisms of ZIKV persistence that can be targeted to restrict ZIKV spread.

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Dengue Virus Immunopathogenesis: Lessons Applicable to the Emergence of Zika Virus

Cited by 39 publications

References 177 publications

Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus

Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus

Host-Virus Interaction of ZIKA Virus in Modulating Disease Pathogenesis

Zika Virus Persistently Infects and Is Basolaterally Released from Primary Human Brain Microvascular Endothelial Cells

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