Viral Infection of Neural Stem Cells

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "General Virology".

Deadline for manuscript submissions: closed (15 April 2021) | Viewed by 20544

Special Issue Editors

Pathogenesis and Control of Chronic Infections, Université de Montpellier, INSERM, EFS, Montpellier, France
Interests: neuro-virology; neuro-inflammation; cognitive dysfunction; blood–brain barrier physiology; emerging and re-emerging viruses
UMR Virology, Anses, Inrae, Enva, Ecole Nationale Vétérinaire d’Alfort, 94700 Maisons-Alfort, France.
Interests: neuro-virology; innate immunity; pathogenesis; Flavivirus; neural stem-cell-derived models; antiviral research; emerging and re-emerging viruses

Special Issue Information

Dear Colleagues,

Viruses that target the brain are responsible for serious diseases such as encephalitis, paralysis, neuro-developmental, and neuro-behavioural disorders. They represent an important medical and social burden due to acute or long-term neurological impairment. Some viruses can cross the placenta and target the developing brain, while others will target more mature glial or neuronal cells. Regardless, there are very limited treatment options. For years, progress in understanding virus-induced neurological disorders has been limited due to the lack of physiologically relevant in vitro models. However, thanks to stem cell technology, highly relevant in vitro 2D and 3D models have recently been developed, especially in humans. Their use in the field of virology has largely been democratized by the recent emergence of Zika virus, declared a global health emergency by OMS in 2016. In this Special Issue, we will focus on research that is at the frontier between neuroscience and virology. More specifically, we will focus on viruses that naturally target neural stem cells as well as on research that is using in vitro 2D/3D models derived from neural stem cells and that is aiming at understanding tropism, pathogenesis, immunity, and the underlying biological mechanisms of viral infection in the central nervous system, as well as identifying antiviral drugs.

Dr. Sara Salinas
Dr. Muriel Coulpier
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neural stem cells
  • neurotropic viruses
  • congenital infections
  • neurodevelopment
  • neuronal and cognitive impairment
  • neuropathogenesis
  • neurogenesis
  • immunity
  • cerebral organoids
  • antiviral drugs

Published Papers (6 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

15 pages, 1732 KiB  
Article
A Rat Model of Prenatal Zika Virus Infection and Associated Long-Term Outcomes
by Morgan L. Sherer, Elise A. Lemanski, Rita T. Patel, Shannon R. Wheeler, Mark S. Parcells and Jaclyn M. Schwarz
Viruses 2021, 13(11), 2298; https://0-doi-org.brum.beds.ac.uk/10.3390/v13112298 - 18 Nov 2021
Cited by 4 | Viewed by 1796
Abstract
Zika virus (ZIKV) is a mosquito-borne flavivirus that became widely recognized due to the epidemic in Brazil in 2015. Since then, there has been nearly a 20-fold increase in the incidence of microcephaly and birth defects seen among women giving birth in Brazil, [...] Read more.
Zika virus (ZIKV) is a mosquito-borne flavivirus that became widely recognized due to the epidemic in Brazil in 2015. Since then, there has been nearly a 20-fold increase in the incidence of microcephaly and birth defects seen among women giving birth in Brazil, leading the Centers for Disease Control and Prevention (CDC) to officially declare a causal link between prenatal ZIKV infection and the serious brain abnormalities seen in affected infants. Here, we used a unique rat model of prenatal ZIKV infection to study three possible long-term outcomes of congenital ZIKV infection: (1) behavior, (2) cell proliferation, survival, and differentiation in the brain, and (3) immune responses later in life. Adult offspring that were prenatally infected with ZIKV exhibited motor deficits in a sex-specific manner, and failed to mount a normal interferon response to a viral immune challenge later in life. Despite undetectable levels of ZIKV in the brain and serum in these offspring at P2, P24, or P60, these results suggest that prenatal exposure to ZIKV results in lasting consequences that could significantly impact the health of the offspring. To help individuals already exposed to ZIKV, as well as be prepared for future outbreaks, we need to understand the full spectrum of neurological and immunological consequences that could arise following prenatal ZIKV infection. Full article
(This article belongs to the Special Issue Viral Infection of Neural Stem Cells)
Show Figures

Figure 1

14 pages, 14546 KiB  
Communication
Transcriptomic Studies Suggest a Coincident Role for Apoptosis and Pyroptosis but Not for Autophagic Neuronal Death in TBEV-Infected Human Neuronal/Glial Cells
by Mazigh Fares, Kamila Gorna, Noémie Berry, Marielle Cochet-Bernoin, François Piumi, Odile Blanchet, Nadia Haddad, Jennifer Richardson and Muriel Coulpier
Viruses 2021, 13(11), 2255; https://0-doi-org.brum.beds.ac.uk/10.3390/v13112255 - 10 Nov 2021
Cited by 4 | Viewed by 1948
Abstract
Tick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, Flavivirus genus, is responsible for neurological symptoms that may cause permanent disability or death. With an incidence on the rise, it is the major arbovirus affecting humans in Central/Northern Europe and North-Eastern Asia. [...] Read more.
Tick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, Flavivirus genus, is responsible for neurological symptoms that may cause permanent disability or death. With an incidence on the rise, it is the major arbovirus affecting humans in Central/Northern Europe and North-Eastern Asia. Neuronal death is a critical feature of TBEV infection, yet little is known about the type of death and the molecular mechanisms involved. In this study, we used a recently established pathological model of TBEV infection based on human neuronal/glial cells differentiated from fetal neural progenitors and transcriptomic approaches to tackle this question. We confirmed the occurrence of apoptotic death in these cultures and further showed that genes involved in pyroptotic death were up-regulated, suggesting that this type of death also occurs in TBEV-infected human brain cells. On the contrary, no up-regulation of major autophagic genes was found. Furthermore, we demonstrated an up-regulation of a cluster of genes belonging to the extrinsic apoptotic pathway and revealed the cellular types expressing them. Our results suggest that neuronal death occurs by multiple mechanisms in TBEV-infected human neuronal/glial cells, thus providing a first insight into the molecular pathways that may be involved in neuronal death when the human brain is infected by TBEV. Full article
(This article belongs to the Special Issue Viral Infection of Neural Stem Cells)
Show Figures

Figure 1

15 pages, 2141 KiB  
Article
Effect of Serial Systemic and Intratumoral Injections of Oncolytic ZIKVBR in Mice Bearing Embryonal CNS Tumors
by Raiane Oliveira Ferreira, Isabela Granha, Rodolfo Sanches Ferreira, Heloisa de Siqueira Bueno, Oswaldo Keith Okamoto, Carolini Kaid and Mayana Zatz
Viruses 2021, 13(10), 2103; https://0-doi-org.brum.beds.ac.uk/10.3390/v13102103 - 19 Oct 2021
Cited by 8 | Viewed by 7302
Abstract
The Zika virus (ZIKV) has shown a promising oncolytic effect against embryonal CNS tumors. However, studies on the effect of different administration routes and the ideal viral load in preclinical models are highly relevant aiming for treatment safety and efficiency. Here, we investigated [...] Read more.
The Zika virus (ZIKV) has shown a promising oncolytic effect against embryonal CNS tumors. However, studies on the effect of different administration routes and the ideal viral load in preclinical models are highly relevant aiming for treatment safety and efficiency. Here, we investigated the effect and effectiveness of different routes of administration, and the number of ZIKVBR injections on tumor tropism, destruction, and side effects. Furthermore, we designed an early-stage human brain organoid co-cultured with embryonal CNS tumors to analyze the ZIKVBR oncolytic effect. We showed that in the mice bearing subcutaneous tumors, the ZIKVBR systemically presented a tropism to the brain. When the tumor was located in the mice’s brain, serial systemic injections presented efficient tumor destruction, with no neurological or other organ injury and increased mice survival. In the human cerebral organoid model co-cultured with embryonal CNS tumor cells, ZIKVBR impaired tumor progression. The gene expression of cytokines and chemokines in both models suggested an enhancement of immune cells recruitment and tumor inflammation after the treatment. These results open new perspectives for virotherapy using the ZIKVBR systemic administration route and multiple doses of low virus load for safe and effective treatment of embryonal CNS tumors, an orphan disease that urges new effective therapies. Full article
(This article belongs to the Special Issue Viral Infection of Neural Stem Cells)
Show Figures

Graphical abstract

Review

Jump to: Research

15 pages, 1072 KiB  
Review
Neural Stem Cells: What Happens When They Go Viral?
by Yashika S. Kamte, Manisha N. Chandwani, Alexa C. Michaels and Lauren A. O’Donnell
Viruses 2021, 13(8), 1468; https://0-doi-org.brum.beds.ac.uk/10.3390/v13081468 - 27 Jul 2021
Cited by 11 | Viewed by 2634
Abstract
Viruses that infect the central nervous system (CNS) are associated with developmental abnormalities as well as neuropsychiatric and degenerative conditions. Many of these viruses such as Zika virus (ZIKV), cytomegalovirus (CMV), and herpes simplex virus (HSV) demonstrate tropism for neural stem cells (NSCs). [...] Read more.
Viruses that infect the central nervous system (CNS) are associated with developmental abnormalities as well as neuropsychiatric and degenerative conditions. Many of these viruses such as Zika virus (ZIKV), cytomegalovirus (CMV), and herpes simplex virus (HSV) demonstrate tropism for neural stem cells (NSCs). NSCs are the multipotent progenitor cells of the brain that have the ability to form neurons, astrocytes, and oligodendrocytes. Viral infections often alter the function of NSCs, with profound impacts on the growth and repair of the brain. There are a wide spectrum of effects on NSCs, which differ by the type of virus, the model system, the cell types studied, and the age of the host. Thus, it is a challenge to predict and define the consequences of interactions between viruses and NSCs. The purpose of this review is to dissect the mechanisms by which viruses can affect survival, proliferation, and differentiation of NSCs. This review also sheds light on the contribution of key antiviral cytokines in the impairment of NSC activity during a viral infection, revealing a complex interplay between NSCs, viruses, and the immune system. Full article
(This article belongs to the Special Issue Viral Infection of Neural Stem Cells)
Show Figures

Figure 1

13 pages, 9602 KiB  
Review
Hearing Loss Caused by HCMV Infection through Regulating the Wnt and Notch Signaling Pathways
by Sheng-Nan Huang, Yue-Peng Zhou, Xuan Jiang, Bo Yang, Han Cheng and Min-Hua Luo
Viruses 2021, 13(4), 623; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040623 - 06 Apr 2021
Cited by 8 | Viewed by 2729
Abstract
Hearing loss is one of the most prevalent sensory disabilities worldwide with huge social and economic burdens. The leading cause of sensorineural hearing loss (SNHL) in children is congenital cytomegalovirus (CMV) infection. Though the implementation of universal screening and early intervention such as [...] Read more.
Hearing loss is one of the most prevalent sensory disabilities worldwide with huge social and economic burdens. The leading cause of sensorineural hearing loss (SNHL) in children is congenital cytomegalovirus (CMV) infection. Though the implementation of universal screening and early intervention such as antiviral or anti-inflammatory ameliorate the severity of CMV-associated diseases, direct and targeted therapeutics is still seriously lacking. The major hurdle for it is that the mechanism of CMV induced SNHL has not yet been well understood. In this review, we focus on the impact of CMV infection on the key players in inner ear development including the Wnt and Notch signaling pathways. Investigations on these interactions may gain new insights into viral pathogenesis and reveal novel targets for therapy. Full article
(This article belongs to the Special Issue Viral Infection of Neural Stem Cells)
Show Figures

Figure 1

9 pages, 231 KiB  
Review
Varicella-Zoster Virus Infection of Neurons Derived from Neural Stem Cells
by Peter G. E. Kennedy and Trine H. Mogensen
Viruses 2021, 13(3), 485; https://0-doi-org.brum.beds.ac.uk/10.3390/v13030485 - 15 Mar 2021
Cited by 7 | Viewed by 3330
Abstract
Varicella-Zoster virus (VZV) is a human herpesvirus that causes varicella (chickenpox) as a primary infection, and, following a variable period of ganglionic latency in neurons, it reactivates to cause herpes zoster (shingles). An analysis of VZV infection in cultures of neural cells, in [...] Read more.
Varicella-Zoster virus (VZV) is a human herpesvirus that causes varicella (chickenpox) as a primary infection, and, following a variable period of ganglionic latency in neurons, it reactivates to cause herpes zoster (shingles). An analysis of VZV infection in cultures of neural cells, in particular when these have been obtained from induced pluripotent stem cells (iPSCs) or neural stem cells consisting of highly purified neuronal cultures, has revealed much data that may be of neurobiological significance. Early studies of VZV infection of mature cultured neural cells were mainly descriptive, but more recent studies in homogeneous neural stem cell cultures have used both neuronal cell markers and advanced molecular technology. Two general findings from such studies have been that (a) VZV infection of neurons is less severe, based on several criteria, than that observed in human fibroblasts, and (b) VZV infection of neurons does not lead to apoptosis in these cells in contrast to apoptosis observed in fibroblastic cells. Insights gained from such studies in human neural stem cells suggest that a less severe initial lytic infection in neurons, which are resistant to apoptosis, is likely to facilitate a pathological pathway to a latent state of the virus in human ganglia. Full article
(This article belongs to the Special Issue Viral Infection of Neural Stem Cells)
Back to TopTop