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

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.

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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

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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.

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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

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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

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A Zika Virus Primary Isolate Induces Neuroinflammation, Compromises the Blood-Brain Barrier, and Upregulates CXCL12 in Adult Macaques

10.1101/850198 ◽

2019 ◽

Author(s):

Antonito T. Panganiban ◽

Robert V. Blair ◽

Julian B. Hattler ◽

Diana G. Bohannon ◽

Myrna C. Bonaldo ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Virus Infection ◽

Brain Damage ◽

Blood Brain Barrier ◽

Zika Virus ◽

Brain Inflammation ◽

Brain Barrier ◽

Blood Brain ◽

The Central Nervous System

AbstractZika virus (ZIKV) is a neurotropic virus that can cause neuropathy in adults and fetal neurologic malformation following infection of pregnant women. We used a nonhuman primate model, the Indian-origin Rhesus macaque (IRM), to gain insight into virus-associated hallmarks of ZIKV-induced adult neuropathy. We find that the virus causes prevalent acute and chronic neuroinflammation and chronic disruption of the blood-brain barrier (BBB) in adult animals. Infection results in significant, targeted, and sustained upregulation of the chemokine, CXCL12, in the central nervous system (CNS). CXCL12 plays a key role both in regulating lymphocyte trafficking through the BBB to the CNS, and in mediating repair of damaged neural tissue including remyelination. Understanding how CXCL12 expression is controlled will likely be of central importance in the definition of ZIKV-associated neuropathy in adults.Author summaryZika virus (ZIKV) is a virus that can cause neurological problems in adults and damage to the fetal brain. Nonhuman primates (NHPs) are usually superior animal models for recapitulating human neurological disease because their brain, nervous system structure and immune response to virus infection are very similar to that of humans. We have studied the effect of ZIKV infection on the adult NHP brain and made several significant observations. Infection resulted in a high incidence of mild to moderate brain inflammation that persisted for a surprisingly long period of time. We also found that the virus disrupted the blood brain barrier, which is important for controlling transport of material from blood to the brain. It appears that the central nervous system expresses a specific substance in response to virus infection called a chemokine. This specific chemokine may be involved in virus-induced inflammation and/or in repair of virus-induced brain damage. Our data are significant since they help in understanding the mechanism of brain damage caused by ZIKV in adults.

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