Zika Virus Pathogenesis: From Early Case Reports to Epidemics

Pardy, Ryan D.; Richer, Martin J.

doi:10.3390/v11100886

Cited by 22 publications

(14 citation statements)

References 59 publications

(121 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed ZIKV-associated dysmyelination within such cultures and determined that the key CNS myelinating cell type, oligodendrocytes, are predominant targets for ZIKV [ 44 ]. The causal link between GBS, a PNS neuropathy, and ZIKV infection in a predominantly demyelinating subtype of the disease is well established [ 12 , 19 , 45 , 85 , 86 ]. Although our prior studies on murine PNS myelinating cultures infected with ZIKV show poor infection of the myelin-forming Schwann cells in the PNS [ 44 ], others have shown that ZIKV infection caused cytopathic effects in Schwann cells resulting in PNS myelin degeneration [ 87 ].…”

Section: Discussionmentioning

confidence: 99%

“…These included neurodevelopmental impairments, grouped under the description “congenital Zika syndrome” (CZS), as well as fetal death. Moreover, later neurodevelopmental abnormalities have been reported, thus emphasizing the need for long-term surveillance [ 3 , 4 , 6 , 12 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. The full spectrum of disease may indeed only become clear over time.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures

Schultz

Cumberworth

et al. 2021

Viruses

View full text Add to dashboard Cite

Understanding how Zika virus (Flaviviridae; ZIKV) affects neural cells is paramount in comprehending pathologies associated with infection. Whilst the effects of ZIKV in neural development are well documented, impact on the adult nervous system remains obscure. Here, we investigated the effects of ZIKV infection in established mature myelinated central nervous system (CNS) cultures. Infection incurred damage to myelinated fibers, with ZIKV-positive cells appearing when myelin damage was first detected as well as axonal pathology, suggesting the latter was a consequence of oligodendroglia infection. Transcriptome analysis revealed host factors that were upregulated during ZIKV infection. One such factor, CCL5, was validated in vitro as inhibiting myelination. Transferred UV-inactivated media from infected cultures did not damage myelin and axons, suggesting that viral replication is necessary to induce the observed effects. These data show that ZIKV infection affects CNS cells even after myelination—which is critical for saltatory conduction and neuronal function—has taken place. Understanding the targets of this virus across developmental stages including the mature CNS, and the subsequent effects of infection of cell types, is necessary to understand effective time frames for therapeutic intervention.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures

Schultz

Cumberworth

et al. 2021

Viruses

View full text Add to dashboard Cite

show abstract

“…West Nile virus (WNV) and Zika virus (ZIKV) are medically important arboviruses that cause severe neurological disease in humans [ 23 , 24 ]. Control of WNV requires robust neuroinflammation and infiltration of peripheral leukocytes into the central nervous system (CNS), mediated by RIPK1 and RIPK3 [ 23 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

The diverse roles of RIP kinases in host-pathogen interactions

Eng

Wemyss

Pearson

2021

Seminars in Cell & Developmental Biology

View full text Add to dashboard Cite

Receptor Interacting Protein Kinases (RIPKs) are cellular signaling molecules that are critical for homeostatic signaling in both communicable and non-communicable disease processes. In particular, RIPK1, RIPK2, RIPK3 and RIPK7 have emerged as key mediators of intracellular signal transduction including inflammation, autophagy and programmed cell death, and are thus essential for the early control of many diverse pathogenic organisms. In this review, we discuss the role of each RIPK in host responses to bacterial and viral pathogens, with a focus on studies that have used pathogen infection models rather than artificial stimulation with purified pathogen associated molecular patterns. We also discuss the intricate mechanisms of host evasion by pathogens that specifically target RIPKs for inactivation, and finally, we will touch on the controversial issue of drug development for kinase inhibitors to treat chronic inflammatory and neurological disorders, and the implications this may have on the outcome of pathogen infections.

show abstract

“…The 2015 ZIKV outbreak was considered as a test case in the context of the PREPARE network, as the pathogenesis of neurologic or immune disease induced by ZIKV is not fully understood. ZIKV is a flavivirus belonging to the Flaviviridae family and had only marginally been researched prior to the 2015 epidemic was minimal (6–8). Outbreaks of ZIKV disease have been recorded in Africa, the Americas, Asia and the Pacific.…”

Section: Introductionmentioning

confidence: 99%

Informing epidemic (research) responses in a timely fashion by knowledge management - a Zika virus use case

Bauch

Pellet²,

Schleicher

et al. 2020

Preprint

View full text Add to dashboard Cite

25The response of pathophysiological research to emerging epidemics often occurs 26 after the epidemic and, as a consequence, has little to no impact on improving 27 patient outcomes or on developing high-quality evidence to inform clinical 28 management strategies during the epidemic. Rapid and informed guidance of 29 epidemic (research) responses to severe infectious disease outbreaks requires quick 30 compilation and integration of existing pathophysiological knowledge. As a case 31 study we chose the Zika virus (ZIKV) outbreak that started in 2015 to develop a 32 proof-of-concept knowledge repository. To extract data from available sources and 33 build a computationally tractable and comprehensive molecular interaction map we 34 applied generic knowledge management software for literature mining, expert 35 knowledge curation, data integration, reporting and visualisation. A multi-disciplinary 36 team of experts, including clinicians, virologists, bioinformaticians and knowledge 37 management specialists, followed a pre-defined workflow for rapid integration and 38 evaluation of available evidence. While conventional approaches usually require 39 months to comb through the existing literature, the initial ZIKV KnowledgeBase 40 (ZIKA KB) was completed within a few weeks. Recently we updated the ZIKA KB 41 with additional curated data from the large amount of literature published since 2016 42 and made it publicly available through a web interface together with a step-by-step 43 guide to ensure reproducibility of the described use case (S4). In addition, a detailed 44 online user manual is provided to enable the ZIKV research community to generate 45 hypotheses, share knowledge, identify knowledge gaps, and interactively explore 46 and interpret data (S5). A workflow for rapid response during outbreaks was 47 threats. The resulting structured biological knowledge is a helpful tool for 50 computational data analysis and generation of predictive models and opens new 51 avenues for infectious disease research. 52 53 Availability: www.zikaknowledgebase.eu 54 55 Funding 56 European Commission's Seventh Framework Research Programme project 57 PREPARE (FP7-Health n°602525) and ZIKALLIANCE (MK, H2020; No 734548). 58 59 Author summary 60 During the recent ZIKV outbreak there was little information about the interactions 61 between Zika virus and the host, however, the massive research response lead to a 62 steep increase in the number of relevant publications within a very short period of 63 time. At the time, there was no structured and comprehensive database available for 64 integrated molecular and physiological data and knowledge about ZIKV infection. 65through the massive amount of existing literature. In addition to providing 74 background information for research, scientific publications can be processed to 75 transform textual information into complex networks, which can be integrated with 76 existing knowledge resources to suggest novel hypotheses that potentially contribute 77 to innovative infectious disease r...

show abstract

Zika Virus Pathogenesis: From Early Case Reports to Epidemics

Cited by 22 publications

References 59 publications

Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures

Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures

The diverse roles of RIP kinases in host-pathogen interactions

Informing epidemic (research) responses in a timely fashion by knowledge management - a Zika virus use case

Contact Info

Product

Resources

About