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Zika Virus and Host Interactions

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A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (30 September 2019) | Viewed by 74272

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Special Issue Editors

Prof. Tom Hobman

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Guest Editor

Department of Cell Biology, University of Alberta, Edmonton, AB T6G 2H7, Canada
Interests: RNA virus; host interactions; RNA interference pathways

Dr. Anil Kumar

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Assistant Editor

Department of Cell Biology, University of Alberta, Edmonton, AB T6G 2H7, Canada
Interests: arboviruses; virus-host interaction; innate immunity

Dr. Daniel Limonta

E-Mail Website
Assistant Editor

Department of Cell Biology, University of Alberta, Edmonton, AB T6G 2H7, Canada
Interests: Zika virus biology; dengue virus pathogenesis; cell death; interferon response

Special Issue Information

Dear Colleagues,

Zika virus is the mosquito-transmitted flavivirus that was responsible for a recent pandemic in the Americas. Brazil was at the epicenter of this outbreak and experienced an inordinate number of babies born with microcephaly and other neurological disorders. In addition to being a teratogenic agent, Zika virus infection is linked to increased risk of Guillain–Barré syndrome in adults. Although the virus was discovered over 70 years ago in Africa, prior to the 2015/2016 outbreak, very little was known about this pathogen. As such, neither specific therapeutic or prophylactic regimens are available to manage the disease. These factors led to a dramatic increase in research activity focused on Zika virus and in particular, development of vaccine candidates which are in various stages of clinical trials. While the pandemic in South and Central America has subsided, many parts of the world remain at risk for near term outbreaks due to the prevelance of mosquito vectors that transmit Zika virus and large dense urban areas with serologically naïve populations. Accordingly, to limit Zika virus-associated disease in future epidemics, it is imperative to further understand how this pathogen interacts with different host cell types.

The aim of this Special Issue of Cells is to showcase the latest research findings that advance our knowledge of how Zika virus targets cellular pathways to allow productive replication and establish persistence. It is anticipated that findings from these studies will lead to a molecular understanding of viral disease and form the basis for novel anti-viral therapies. We welcome submissions from the community that focus on all aspects of Zika virus–host interactions.

Prof. Tom Hobman
Dr. Anil Kumar
Dr. Daniel Limonta
Guest Editors

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Keywords

Zika virus
virus–host interactions
pathogenesis
anti-viral signaling
replication
immune response
virus evolution

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Published Papers (14 papers)

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Editorial

Jump to: Research, Review

5 pages, 520 KiB

Open AccessEditorial

Zika Virus and Host Interactions: From the Bench to the Bedside and Beyond

by Daniel Limonta and Tom C. Hobman

Cells 2020, 9(11), 2463; https://doi.org/10.3390/cells9112463 - 12 Nov 2020

Cited by 4 | Viewed by 2301

Abstract

Before the emergence of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causative agent of the current COVID-19 (coronavirus disease 2019) pandemic [...] Full article

(This article belongs to the Special Issue Zika Virus and Host Interactions)

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Research

Jump to: Editorial, Review

15 pages, 3184 KiB

Open AccessArticle

RIG-I Plays a Dominant Role in the Induction of Transcriptional Changes in Zika Virus-Infected Cells, which Protect from Virus-Induced Cell Death

by Mirjam Schilling, Anne Bridgeman, Nicki Gray, Jonny Hertzog, Philip Hublitz, Alain Kohl and Jan Rehwinkel

Cells 2020, 9(6), 1476; https://doi.org/10.3390/cells9061476 - 16 Jun 2020

Cited by 23 | Viewed by 4800

Abstract

The Zika virus (ZIKV) has received much attention due to an alarming increase in cases of neurological disorders including congenital Zika syndrome associated with infection. To date, there is no effective treatment available. An immediate response by the innate immune system is crucial for effective control of the virus. Using CRISPR/Cas9-mediated knockouts in A549 cells, we investigated the individual contributions of the RIG-I-like receptors MDA5 and RIG-I to ZIKV sensing and control of this virus by using a Brazilian ZIKV strain. We show that RIG-I is the main sensor for ZIKV in A549 cells. Surprisingly, we observed that loss of RIG-I and consecutive type I interferon (IFN) production led to virus-induced apoptosis. ZIKV non-structural protein NS5 was reported to interfere with type I IFN receptor signaling. Additionally, we show that ZIKV NS5 inhibits type I IFN induction. Overall, our study highlights the importance of RIG-I-dependent ZIKV sensing for the prevention of virus-induced cell death and shows that NS5 inhibits the production of type I IFN. Full article

(This article belongs to the Special Issue Zika Virus and Host Interactions)

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15 pages, 2795 KiB

Open AccessArticle

Zika Virus Infects Human Placental Mast Cells and the HMC-1 Cell Line, and Triggers Degranulation, Cytokine Release and Ultrastructural Changes

by Kíssila Rabelo, Antônio José da Silva Gonçalves, Luiz José de Souza, Anna Paula Sales, Sheila Maria Barbosa de Lima, Gisela Freitas Trindade, Bianca Torres Ciambarella, Natália Recardo Amorim Tasmo, Bruno Lourenço Diaz, Jorge José de Carvalho, Márcia Pereira de Oliveira Duarte and Marciano Viana Paes

Cells 2020, 9(4), 975; https://doi.org/10.3390/cells9040975 - 16 Apr 2020

Cited by 13 | Viewed by 4309

Abstract

Zika virus (ZIKV) is an emergent arthropod-borne virus whose outbreak in Brazil has brought major public health problems. Infected individuals have different symptoms, including rash and pruritus, which can be relieved by the administration of antiallergics. In the case of pregnant women, ZIKV can cross the placenta and infect the fetus leading to congenital defects. We have identified that mast cells in the placentae of patients who had Zika during pregnancy can be infected. This led to our investigation on the possible role of mast cells during a ZIKV infection, using the HMC-1 cell line. We analyzed their permissiveness to infection, release of mediators and ultrastructural changes. Flow cytometry detection of ZIKV-NS1 expression 24 h post infection in 45.3% of cells showed that HMC-1 cells are permissive to ZIKV infection. Following infection, β-hexosaminidase was measured in the supernatant of the cells with a notable release at 30 min. In addition, an increase in TNF-α, IL-6, IL-10 and VEGF levels were measured at 6 h and 24 h post infection. Lastly, different intracellular changes were observed in an ultrastructural analysis of infected cells. Our findings suggest that mast cells may represent an important source of mediators that can activate other immune cell types during a ZIKV infection, which has the potential to be a major contributor in the spread of the virus in cases of vertical transmission. Full article

(This article belongs to the Special Issue Zika Virus and Host Interactions)

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Graphical abstract

20 pages, 34643 KiB

Open AccessArticle

Flavivirus Nonstructural Protein NS5 Dysregulates HSP90 to Broadly Inhibit JAK/STAT Signaling

by Justin A. Roby, Katharina Esser-Nobis, Elyse C. Dewey-Verstelle, Marian R. Fairgrieve, Johannes Schwerk, Amy Y. Lu, Frank W. Soveg, Emily A. Hemann, Lauren D. Hatfield, Brian C. Keller, Alexander Shapiro, Adriana Forero, Jennifer E. Stencel-Baerenwald, Ram Savan and Michael Gale, Jr.

Cells 2020, 9(4), 899; https://doi.org/10.3390/cells9040899 - 7 Apr 2020

Cited by 33 | Viewed by 6104

Abstract

Pathogenic flaviviruses antagonize host cell Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling downstream of interferons α/β. Here, we show that flaviviruses inhibit JAK/STAT signaling induced by a wide range of cytokines beyond interferon, including interleukins. This broad inhibition was mapped to viral nonstructural protein 5 (NS5) binding to cellular heat shock protein 90 (HSP90), resulting in reduced Janus kinase–HSP90 interaction and thus destabilization of unchaperoned JAKs (and other kinase clients) of HSP90 during infection by Zika virus, West Nile virus, and Japanese encephalitis virus. Our studies implicate viral dysregulation of HSP90 and the JAK/STAT pathway as a critical determinant of cytokine signaling control during flavivirus infection. Full article

(This article belongs to the Special Issue Zika Virus and Host Interactions)

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18 pages, 5663 KiB

Open AccessArticle

Network of Interactions between ZIKA Virus Non-Structural Proteins and Human Host Proteins

by Volha A. Golubeva, Thales C. Nepomuceno, Giuliana de Gregoriis, Rafael D. Mesquita, Xueli Li, Sweta Dash, Patrícia P. Garcez, Guilherme Suarez-Kurtz, Victoria Izumi, John Koomen, Marcelo A. Carvalho and Alvaro N. A. Monteiro

Cells 2020, 9(1), 153; https://doi.org/10.3390/cells9010153 - 8 Jan 2020

Cited by 21 | Viewed by 6118

Abstract

The Zika virus (ZIKV) is a mosquito-borne Flavivirus and can be transmitted through an infected mosquito bite or through human-to-human interaction by sexual activity, blood transfusion, breastfeeding, or perinatal exposure. After the 2015–2016 outbreak in Brazil, a strong link between ZIKV infection and microcephaly emerged. ZIKV specifically targets human neural progenitor cells, suggesting that proteins encoded by ZIKV bind and inactivate host cell proteins, leading to microcephaly. Here, we present a systematic annotation of interactions between human proteins and the seven non-structural ZIKV proteins corresponding to a Brazilian isolate. The interaction network was generated by combining tandem-affinity purification followed by mass spectrometry with yeast two-hybrid screens. We identified 150 human proteins, involved in distinct biological processes, as interactors to ZIKV non-structural proteins. Our interacting network is composed of proteins that have been previously associated with microcephaly in human genetic disorders and/or animal models. Further, we show that the protein inhibitor of activated STAT1 (PIAS1) interacts with NS5 and modulates its stability. This study builds on previously published interacting networks of ZIKV and genes related to autosomal recessive primary microcephaly to generate a catalog of human cellular targets of ZIKV proteins implicated in processes related to microcephaly in humans. Collectively, these data can be used as a resource for future characterization of ZIKV infection biology and help create a basis for the discovery of drugs that may disrupt the interaction and reduce the health damage to the fetus. Full article

(This article belongs to the Special Issue Zika Virus and Host Interactions)

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32 pages, 8616 KiB

Open AccessArticle

Participation of Extracellular Vesicles from Zika-Virus-Infected Mosquito Cells in the Modification of Naïve Cells’ Behavior by Mediating Cell-to-Cell Transmission of Viral Elements

by Pedro Pablo Martínez-Rojas, Elizabeth Quiroz-García, Verónica Monroy-Martínez, Lourdes Teresa Agredano-Moreno, Luis Felipe Jiménez-García and Blanca H. Ruiz-Ordaz

Cells 2020, 9(1), 123; https://doi.org/10.3390/cells9010123 - 4 Jan 2020

Cited by 34 | Viewed by 6196

Abstract

To date, no safe vaccine or antivirals for Zika virus (ZIKV) infection have been found. The pathogenesis of severe Zika, where host and viral factors participate, remains unclear. For the control of Zika, it is important to understand how ZIKV interacts with different host cells. Knowledge of the targeted cellular pathways which allow ZIKV to productively replicate and/or establish prolonged viral persistence contributes to novel vaccines and therapies. Monocytes and endothelial vascular cells are the main ZIKV targets. During the infection process, cells are capable of releasing extracellular vesicles (EVs). EVs are mediators of intercellular communication. We found that mosquito EVs released from ZIKV-infected (C6/36) cells carry viral RNA and ZIKV-E protein and are able to infect and activate naïve mosquito and mammalian cells. ZIKV C6/36 EVs promote the differentiation of naïve monocytes and induce a pro-inflammatory state with tumor necrosis factor-alpha (TNF-α) mRNA expression. ZIKV C6/36 EVs participate in endothelial vascular cell damage by inducing coagulation (TF) and inflammation (PAR-1) receptors at the endothelial surface of the cell membranes and promote a pro-inflammatory state with increased endothelial permeability. These data suggest that ZIKV C6/36 EVs may contribute to the pathogenesis of ZIKV infection in human hosts. Full article

(This article belongs to the Special Issue Zika Virus and Host Interactions)

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15 pages, 1633 KiB

Open AccessArticle

The Envelope Residues E152/156/158 of Zika Virus Influence the Early Stages of Virus Infection in Human Cells

by Sandra Bos, Wildriss Viranaicken, Etienne Frumence, Ge Li, Philippe Desprès, Richard Y. Zhao and Gilles Gadea

Cells 2019, 8(11), 1444; https://doi.org/10.3390/cells8111444 - 15 Nov 2019

Cited by 11 | Viewed by 3839

Abstract

Emerging infections of mosquito-borne Zika virus (ZIKV) pose an increasing threat to human health, as documented over the recent years in South Pacific islands and the Americas in recent years. To better understand molecular mechanisms underlying the increase in human cases with severe pathologies, we recently demonstrated the functional roles of structural proteins capsid (C), pre-membrane (prM), and envelop (E) of ZIKV epidemic strains with the initiation of viral infection in human cells. Specifically, we found that the C-prM region contributes to permissiveness of human host cells to ZIKV infection and ZIKV-induced cytopathic effects, whereas the E protein is associated with viral attachment and early infection. In the present study, we further characterize ZIKV E proteins by investigating the roles of residues isoleucine 152 (Ile152), threonine 156 (Thr156), and histidine 158 (His158) (i.e., the E-152/156/158 residues), which surround a unique N-glycosylation site (E-154), in permissiveness of human host cells to epidemic ZIKV infection. For comparison purpose, we generated mutant molecular clones of epidemic BeH819015 (BR15) and historical MR766-NIID (MR766) strains that carry each other’s E-152/156/158 residues, respectively. We observed that the BR15 mutant containing the E-152/156/158 residues from MR766 was less infectious in A549-Dual™ cells than parental virus. In contrast, the MR766 mutant containing E-152/156/158 residues from BR15 displayed increased infectivity. The observed differences in infectivity were, however, not correlated with changes in viral binding onto host-cells or cellular responses to viral infection. Instead, the E-152/156/158 residues from BR15 were associated with an increased efficiency of viral membrane fusion inside infected cells due to conformational changes of E protein that enhance exposure of the fusion loop. Our data highlight an important contribution of E-152/156/158 residues to the early steps of ZIKV infection in human cells. Full article

(This article belongs to the Special Issue Zika Virus and Host Interactions)

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18 pages, 9109 KiB

Open AccessArticle

Route of Infection Influences Zika Virus Shedding in a Guinea Pig Model

by Ashley E. Saver, Stephanie A. Crawford, Jonathan D. Joyce and Andrea S. Bertke

Cells 2019, 8(11), 1437; https://doi.org/10.3390/cells8111437 - 14 Nov 2019

Cited by 8 | Viewed by 3158

Abstract

Due to the recent epidemic of Zika virus (ZIKV) infection and resulting sequelae, as well as concerns about both the sexual and vertical transmission of the virus, renewed attention has been paid to the pathogenesis of this unique arbovirus. Numerous small animal models have been used in various ZIKV pathogenicity studies, however, they are often performed using immunodeficient or immunosuppressed animals, which may impact disease progression in a manner not relevant to immunocompetent humans. The use of immunocompetent animal models, such as macaques, is constrained by small sample sizes and the need for specialized equipment/staff. Here we report the establishment of ZIKV infection in an immunocompetent small animal model, the guinea pig, using both subcutaneous and vaginal routes of infection to mimic mosquito-borne and sexual transmission. Guinea pigs developed clinical signs consistent with mostly asymptomatic and mild disease observed in humans. We demonstrate that the route of infection does not significantly alter viral tissue tropism but does impact mucosal shedding mechanics. We also demonstrate persistent infection in sensory and autonomic ganglia, identifying a previously unrecognized niche of viral persistence that could contribute to viral shedding in secretions. We conclude that the guinea pig represents a useful and relevant model for ZIKV pathogenesis. Full article

(This article belongs to the Special Issue Zika Virus and Host Interactions)

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19 pages, 5035 KiB

Open AccessArticle

The ZIKA Virus Delays Cell Death Through the Anti-Apoptotic Bcl-2 Family Proteins

by Jonathan Turpin, Etienne Frumence, Philippe Desprès, Wildriss Viranaicken and Pascale Krejbich-Trotot

Cells 2019, 8(11), 1338; https://doi.org/10.3390/cells8111338 - 29 Oct 2019

Cited by 16 | Viewed by 5282

Abstract

Zika virus (ZIKV) is an emerging human mosquito-transmitted pathogen of global concern, known to be associated with complications such as congenital defects and neurological disorders in adults. ZIKV infection is associated with induction of cell death. However, previous studies suggest that the virally induced apoptosis occurs at a slower rate compared to the course of viral production. In this present study, we investigated the capacity of ZIKV to delay host cell apoptosis. We provide evidence that ZIKV has the ability to interfere with apoptosis whether it is intrinsically or extrinsically induced. In cells expressing viral replicon-type constructions, we show that this control is achieved through replication. Finally, our work highlights an important role for anti-apoptotic Bcl-2 family protein in the ability of ZIKV to control apoptotic pathways, avoiding premature cell death and thereby promoting virus replication in the host-cell. Full article

(This article belongs to the Special Issue Zika Virus and Host Interactions)

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21 pages, 10534 KiB

Open AccessArticle

Syncytiotrophoblast of Placentae from Women with Zika Virus Infection Has Altered Tight Junction Protein Expression and Increased Paracellular Permeability

by Jael Miranda, Dolores Martín-Tapia, Yolotzin Valdespino-Vázquez, Lourdes Alarcón, Aurora Espejel-Nuñez, Mario Guzmán-Huerta, José Esteban Muñoz-Medina, Mineko Shibayama, Bibiana Chávez-Munguía, Guadalupe Estrada-Gutiérrez, Samuel Lievano, Juan Ernesto Ludert and Lorenza González-Mariscal

Cells 2019, 8(10), 1174; https://doi.org/10.3390/cells8101174 - 29 Sep 2019

Cited by 44 | Viewed by 6526

Abstract

The cytotrophoblast of human placenta transitions into an outer multinucleated syncytiotrophoblast (STB) layer that covers chorionic villi which are in contact with maternal blood in the intervillous space. During pregnancy, the Zika virus (ZIKV) poses a serious prenatal threat. STB cells are resistant to ZIKV infections, yet placental cells within the mesenchyme of chorionic villi are targets of ZIKV infection. We seek to determine whether ZIKV can open the paracellular pathway of STB cells. This route is regulated by tight junctions (TJs) which are present in the uppermost portion of the lateral membranes of STB cells. We analyzed the paracellular permeability and expression of E-cadherin, occludin, JAMs –B and –C, claudins -1, -3, -4, -5 and -7, and ZO-1, and ZO-2 in the STB of placentae from ZIKV-infected and non-infected women. In ZIKV-infected placentae, the pattern of expression of TJ proteins was preserved, but the amount of claudin-4 diminished. Placentae from ZIKV-infected women were permeable to ruthenium red, and had chorionic villi with a higher mean diameter and Hofbauer hyperplasia. Finally, ZIKV added to the basolateral surface of a trophoblast cell line reduced the transepithelial electrical resistance. These results suggest that ZIKV can open the paracellular pathway of STB cells. Full article

(This article belongs to the Special Issue Zika Virus and Host Interactions)

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16 pages, 2291 KiB

Open AccessArticle

Interplay between Zika Virus and Peroxisomes during Infection

by Cheung Pang Wong, Zaikun Xu, Shangmei Hou, Daniel Limonta, Anil Kumar, Christopher Power and Tom C. Hobman

Cells 2019, 8(7), 725; https://doi.org/10.3390/cells8070725 - 15 Jul 2019

Cited by 23 | Viewed by 4525

Abstract

Zika virus (ZIKV) has emerged as an important human pathogen that can cause congenital defects in the fetus and neurological conditions in adults. The interferon (IFN) system has proven crucial in restricting ZIKV replication and pathogenesis. The canonical IFN response is triggered by the detection of viral RNA through RIG-I like receptors followed by activation of the adaptor protein MAVS on mitochondrial membranes. Recent studies have shown that a second organelle, peroxisomes, also function as a signaling platforms for the IFN response. Here, we investigated how ZIKV infection affects peroxisome biogenesis and antiviral signaling. We show that ZIKV infection depletes peroxisomes in human fetal astrocytes, a brain cell type that can support persistent infection. The peroxisome biogenesis factor PEX11B was shown to inhibit ZIKV replication, likely by increasing peroxisome numbers and enhancing downstream IFN-dependent antiviral signaling. Given that peroxisomes play critical roles in brain development and nerve function, our studies provide important insights into the roles of peroxisomes in regulating ZIKV infection and potentially neuropathogenesis. Full article

(This article belongs to the Special Issue Zika Virus and Host Interactions)

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Review

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17 pages, 2065 KiB

Open AccessReview

The Cellular Impact of the ZIKA Virus on Male Reproductive Tract Immunology and Physiology

by Raquel das Neves Almeida, Heloisa Antoniella Braz-de-Melo, Igor de Oliveira Santos, Rafael Corrêa, Gary P. Kobinger and Kelly Grace Magalhaes

Cells 2020, 9(4), 1006; https://doi.org/10.3390/cells9041006 - 18 Apr 2020

Cited by 22 | Viewed by 8272

Abstract

Zika virus (ZIKV) has been reported by several groups as an important virus causing pathological damage in the male reproductive tract. ZIKV can infect and persist in testicular somatic and germ cells, as well as spermatozoa, leading to cell death and testicular atrophy. ZIKV has also been detected in semen samples from ZIKV-infected patients. This has huge implications for human reproduction. Global scientific efforts are being applied to understand the mechanisms related to arboviruses persistency, pathogenesis, and host cellular response to suggest a potential target to develop robust antiviral therapeutics and vaccines. Here, we discuss the cellular modulation of the immunologic and physiologic properties of the male reproductive tract environment caused by arboviruses infection, focusing on ZIKV. We also present an overview of the current vaccine effects and therapeutic targets against ZIKV infection that may impact the testis and male fertility. Full article

(This article belongs to the Special Issue Zika Virus and Host Interactions)

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15 pages, 1404 KiB

Open AccessReview

The Potential Role of the ZIKV NS5 Nuclear Spherical-Shell Structures in Cell Type-Specific Host Immune Modulation during ZIKV Infection

by Min Jie Alvin Tan, Kitti Wing Ki Chan, Ivan H. W. Ng, Sean Yao Zu Kong, Chin Piaw Gwee, Satoru Watanabe and Subhash G. Vasudevan

Cells 2019, 8(12), 1519; https://doi.org/10.3390/cells8121519 - 26 Nov 2019

Cited by 15 | Viewed by 5062

Abstract

The Zika virus (ZIKV) non-structural protein 5 (NS5) plays multiple viral and cellular roles during infection, with its primary role in virus RNA replication taking place in the cytoplasm. However, immunofluorescence assay studies have detected the presence of ZIKV NS5 in unique spherical shell-like structures in the nuclei of infected cells, suggesting potentially important cellular roles of ZIKV NS5 in the nucleus. Hence ZIKV NS5′s subcellular distribution and localization must be tightly regulated during ZIKV infection. Both ZIKV NS5 expression or ZIKV infection antagonizes type I interferon signaling, and induces a pro-inflammatory transcriptional response in a cell type-specific manner, but the mechanisms involved and the role of nuclear ZIKV NS5 in these cellular functions has not been elucidated. Intriguingly, these cells originate from the brain and placenta, which are also organs that exhibit a pro-inflammatory signature and are known sites of pathogenesis during ZIKV infection in animal models and humans. Here, we discuss the regulation of the subcellular localization of the ZIKV NS5 protein, and its putative role in the induction of an inflammatory response and the occurrence of pathology in specific organs during ZIKV infection. Full article

(This article belongs to the Special Issue Zika Virus and Host Interactions)

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11 pages, 431 KiB

Open AccessFeature PaperReview

Protective to a T: The Role of T Cells during Zika Virus Infection

by Ryan D. Pardy and Martin J. Richer

Cells 2019, 8(8), 820; https://doi.org/10.3390/cells8080820 - 3 Aug 2019

Cited by 29 | Viewed by 6044

Abstract

CD4 and CD8 T cells are an important part of the host’s capacity to defend itself against viral infections. During flavivirus infections, T cells have been implicated in both protective and pathogenic responses. Given the recent emergence of Zika virus (ZIKV) as a prominent global health threat, the question remains as to how T cells contribute to anti-ZIKV immunity. Furthermore, high homology between ZIKV and other, co-circulating flaviviruses opens the possibility of positive or negative effects of cross-reactivity due to pre-existing immunity. In this review, we will discuss the CD4 and CD8 T cell responses to ZIKV, and the lessons we have learned from both mouse and human infections. In addition, we will consider the possibility of whether T cells, in the context of flavivirus-naïve and flavivirus-immune subjects, play a role in promoting ZIKV pathogenesis during infection. Full article

(This article belongs to the Special Issue Zika Virus and Host Interactions)

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