Therapeutic Approaches for Zika Virus Infection of the Nervous System

Flaviviruses such as Zika virus and West Nile virus have the potential to cause severe neuropathology if they invade the central nervous system. The type I interferon response is well characterized as contributing to control of flavivirus-induced neuropathogenesis. However, the interferon-stimulated gene (ISG) effectors that confer these neuroprotective effects are less well studied. Here, we used an ISG expression screen to identify Shiftless (SHFL, C19orf66) as a potent inhibitor of diverse positive-stranded RNA viruses, including multiple members of the Flaviviridae (Zika, West Nile, dengue, yellow fever, and hepatitis C viruses). In cultured cells, SHFL functions as a viral RNA-binding protein that inhibits viral replication at a step after primary translation of the incoming genome. The murine ortholog, Shfl, is expressed constitutively in multiple tissues, including the central nervous system. In a mouse model of Zika virus infection, Shfl−/− knockout mice exhibit reduced survival, exacerbated neuropathological outcomes, and increased viral replication in the brain and spinal cord. These studies demonstrate that Shfl is an important antiviral effector that contributes to host protection from Zika virus infection and virus-induced neuropathological disease.

Download Full-text

Correlation between Zika virus and microcephaly as a consequence of congenital infection

10.5327/1516-3180.629 ◽

2021 ◽

Author(s):

Ana Flávia Silva Castro ◽

Natália Barros Salgado Vieira ◽

Sarah Joanny da Silva Pereira

Keyword(s):

Nervous System ◽

Virus Infection ◽

Zika Virus ◽

Complex Disease ◽

Congenital Infection ◽

Virus Infections ◽

Zika Virus Infection ◽

The Central Nervous System ◽

Neurological Effects ◽

The Relationship

Introduction: The Zika virus (ZIKV) is an arbovirus of RNA, whose transmission is mainly vector - by mosquitoes of the genus Aedes - but it also occurs through sexual, blood and transplacental transmission, with the last mentioned it was possible to verify serious neurological effects in the epidemic in South America, especially in Brazil, between 2015 and 2016. Objectives: To analyze the relationship between Zika virus infection and microcephaly in recent scientific literature. Methodology: Refers to a bibliographic review in the databases SciELO, LILACS and MEDLINE / Pubmed, with the terms “zika virus”, “infection” and “microcephaly” correlated in Portuguese and in English; 78 articles were found, but only 7 followed for analysis. Articles published more than 5 years ago and out of the proposed theme were disregarded. Results: The Zika virus, although similar to the dengue and chikungunya virus, it has a tendency to cause damage to the central nervous system such as Guillain-Barré Syndrome. However, the association between microcephaly and ZIKV started to be more observed through the increase of the disease among fetuses and newborns of mothers who had been infected during the gestational phase in the epidemic that happened in Brazil. It is known that the development of the nervous system is the product of processes of high proliferation and cellular differentiation, in which even small errors generate dangerous impacts, and it is during this period that ZIKV affects the CNS of the fetus. The disease is characterized by the reduction of the brain perimeter, in this context, is a consequence of abnormalities influenced by the virus. Conclusions: Microcephaly is a complex disease; therefore, it is necessary to emphasize the importance of primary care and other spheres for monitoring Zika virus infections, prenatal care and constant psychosocial monitoring. Furthermore, it is necessary to understand the relevance of studies about ZIKV and microcephaly, and to encourage scientific production in this area.

Download Full-text

Central Nervous System Effects of Intrauterine Zika Virus Infection: A Pictorial Review

Radiographics ◽

10.1148/rg.2017170023 ◽

2017 ◽

Vol 37 (6) ◽

pp. 1840-1850 ◽

Cited By ~ 15

Author(s):

Bianca Guedes Ribeiro ◽

Heron Werner ◽

Flávia P. P. L. Lopes ◽

L. Celso Hygino da Cruz ◽

Tatiana M. Fazecas ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Virus Infection ◽

Zika Virus ◽

Zika Virus Infection ◽

Pictorial Review

Download Full-text

Invited Commentary on “Central Nervous System Effects of Intrauterine Zika Virus Infection”

Radiographics ◽

10.1148/rg.2017170164 ◽

2017 ◽

Vol 37 (6) ◽

pp. 1850-1853 ◽

Cited By ~ 1

Author(s):

Deborah Levine

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Virus Infection ◽

Zika Virus ◽

Zika Virus Infection

Download Full-text

Zika Virus Infection in the Central Nervous System and Female Genital Tract

Emerging Infectious Diseases ◽

10.3201/eid2212.161280 ◽

2016 ◽

Vol 22 (12) ◽

pp. 2228-2230 ◽

Cited By ~ 51

Author(s):

Emanuele Nicastri ◽

Concetta Castilletti ◽

Pietro Balestra ◽

Simonetta Galgani ◽

Giuseppe Ippolito

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Virus Infection ◽

Zika Virus ◽

Genital Tract ◽

Female Genital Tract ◽

Zika Virus Infection ◽

The Central Nervous System ◽

Female Genital

Download Full-text

Zika virus infection of the central nervous system of mice

Archives of Virology ◽

10.1007/bf01249709 ◽

1971 ◽

Vol 35 (2-3) ◽

pp. 183-193 ◽

Cited By ~ 142

Author(s):

T. M. Bell ◽

E. J. Field ◽

H. K. Narang

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Virus Infection ◽

Zika Virus ◽

Zika Virus Infection ◽

The Central Nervous System

Download Full-text

Nervous System Injury and Neuroimaging of Zika Virus Infection

Frontiers in Neurology ◽

10.3389/fneur.2018.00227 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 5

Author(s):

Shanshan Wu ◽

Yu Zeng ◽

Alexander Lerner ◽

Bo Gao ◽

Meng Law

Keyword(s):

Nervous System ◽

Virus Infection ◽

Zika Virus ◽

Zika Virus Infection

Download Full-text

Evaluation of Possible Consequences of Zika Virus Infection in the Developing Nervous System

Molecular Neurobiology ◽

10.1007/s12035-017-0442-5 ◽

2017 ◽

Vol 55 (2) ◽

pp. 1620-1629 ◽

Cited By ~ 4

Author(s):

Lais Takata Walter ◽

Guilherme Shigueto Vilar Higa ◽

Juliane Midori Ikebara ◽

Danila Vedovello ◽

Felipe Scassi Salvador ◽

...

Keyword(s):

Nervous System ◽

Virus Infection ◽

Zika Virus ◽

Zika Virus Infection ◽

Developing Nervous System

Download Full-text

Congenital Zika Virus Infection Paradigm: What is in the Wardrobe? A Narrative Review

East Africa Science ◽

10.24248/easci.v1i1.4 ◽

2019 ◽

Vol 1 (1) ◽

pp. 49-56

Author(s):

Mariam M. Mirambo ◽

Lucas Matemba ◽

Mtebe Majigo ◽

Stephen E. Mshana

Keyword(s):

Virus Infection ◽

Neural Tube ◽

Zika Virus ◽

English Language ◽

Case Reports ◽

Case Series ◽

Epidemiological Studies ◽

Ocular Manifestations ◽

Zika Virus Infection ◽

N 93

Background: Zika virus infection during pregnancy has been recently associated with congenital microcephaly and other severe neural tube defects. However, the magnitude of confirmed cases and the scope of these anomalies have not been extensively documented. This review focuses on the magnitude of laboratory-confirmed congenital Zika virus cases among probable cases and describing the patterns of congenital anomalies allegedly caused by the Zika virus, information which will inform further research in this area. Methods: We conducted a literature search for English-language articles about congenital Zika virus infection using online electronic databases (PubMed/MEDLINE, POPLINE, Embase, Google Scholar, and Web of Knowledge). The search terms used were, “zika”, “pregnancy”, [year], “microcephaly”, “infants”, “children”, “neonates”, “foetuses”, “neural tube defect”, and “CNS manifestations” in different combinations. All articles reporting cases or case series between January 2015 and December 2016 were included. Data were entered into a Microsoft Excel database and analysed to obtain proportions of the confirmed cases and patterns of anomalies. Results: A total of 24 articles (11 case series, 9 case reports, and 4 others) were found to be eligible and included in this review. These articles reported 919 cases, with or without microcephaly, presumed to have congenital Zika virus infection. Of these cases, 884 (96.2%) had microcephaly. Of the 884 cases of microcephaly, 783 (88.6%) were tested for Zika virus infection, and 216 (27.6%; 95% confidence interval, 24.5% to 30.8%) were confirmed to be Zika virus-positive. In addition to microcephaly, other common abnormalities reported – out of 442 cases investigated – were calcifications of brain tissue (n=240, 54.3%), ventriculomegaly (n=93, 20.8%), cerebellar hypoplasia (n=52, 11.7%), and ocular manifestations (n=46, 10.4%). Conclusion: Based on the available literature, Zika virus infection during pregnancy might lead to a wide array of outcomes other than microcephaly. There is a need for more epidemiological studies in Zika-endemic areas, particularly in Africa, to ascertain the role of Zika virus in causing congenital neurological defects.

Download Full-text