Neurocognitive impacts of arbovirus infections

Clé, Marion; Eldin, Patrick; Briant, Laurence; Lannuzel, Annie; Simonin, Yannick; Perre, Philippe Van de; Cabie, André; Salinas, Sara

doi:10.1186/s12974-020-01904-3

Cited by 40 publications

(40 citation statements)

References 196 publications

(243 reference statements)

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“…Arthritogenic and neurotropic alphaviruses continue to spread around the world, leading to an increase in infections and, consequently, in the occurrence of associated arthralgia and neurological disorders [13,40]. Some arboviruses are now well described for their ability to access the CNS and cause short-and long-term neuropathology, potentially due to acute or chronic inflammatory states [40]. Neurological complications have been described in CHIKV-infected patients, in particular in children and the elderly.…”

Section: Discussionmentioning

confidence: 99%

Mayaro Virus Infects Human Brain Cells and Induces a Potent Antiviral Response in Human Astrocytes

Bengue

Ferraris

Barthélémy

et al. 2021

Viruses

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Mayaro virus (MAYV) and chikungunya virus (CHIKV) are known for their arthrotropism, but accumulating evidence shows that CHIKV infections are occasionally associated with serious neurological complications. However, little is known about the capacity of MAYV to invade the central nervous system (CNS). We show that human neural progenitors (hNPCs), pericytes and astrocytes are susceptible to MAYV infection, resulting in the production of infectious viral particles. In primary astrocytes, MAYV, and to a lesser extent CHIKV, elicited a strong antiviral response, as demonstrated by an increased expression of several interferon-stimulated genes, including ISG15, MX1 and OAS2. Infection with either virus led to an enhanced expression of inflammatory chemokines, such as CCL5, CXCL10 and CXCL11, whereas MAYV induced higher levels of IL-6, IL-12 and IL-15 in these cells. Moreover, MAYV was more susceptible than CHIKV to the antiviral effects of both type I and type II interferons. Taken together, this study shows that although MAYV and CHIKV are phylogenetically related, they induce different types of antiviral responses in astrocytes. This work is the first to evaluate the potential neurotropism of MAYV and shows that brain cells and particularly astrocytes and hNPCs are permissive to MAYV, which, consequently, could lead to MAYV-induced neuropathology.

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Section: Discussionmentioning

confidence: 99%

Mayaro Virus Infects Human Brain Cells and Induces a Potent Antiviral Response in Human Astrocytes

Bengue

Ferraris

Barthélémy

et al. 2021

Viruses

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“…Additionally, the vast majority of viral infections present at least one neurological symptom during the acute phase, which can lead to neurological, behavioral, and cognitive sequelae months after the initial infection [ 2 , 6 ]. A recent report demonstrated that children (0.5–8 years) with severe viral CNS infections show enhanced risk of psychotic illness when they reach young adulthood [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Viral and Prion Infections Associated with Central Nervous System Syndromes in Brazil

Sousa

Santos

Paula

et al. 2021

Viruses

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Virus-induced infections of the central nervous system (CNS) are among the most serious problems in public health and can be associated with high rates of morbidity and mortality, mainly in low- and middle-income countries, where these manifestations have been neglected. Typically, herpes simplex virus 1 and 2, varicella-zoster, and enterovirus are responsible for a high number of cases in immunocompetent hosts, whereas other herpesviruses (for example, cytomegalovirus) are the most common in immunocompromised individuals. Arboviruses have also been associated with outbreaks with a high burden of neurological disorders, such as the Zika virus epidemic in Brazil. There is a current lack of understanding in Brazil about the most common viruses involved in CNS infections. In this review, we briefly summarize the most recent studies and findings associated with the CNS, in addition to epidemiological data that provide extensive information on the circulation and diversity of the most common neuro-invasive viruses in Brazil. We also highlight important aspects of the prion-associated diseases. This review provides readers with better knowledge of virus-associated CNS infections. A deeper understanding of these infections will support the improvement of the current surveillance strategies to allow the timely monitoring of the emergence/re-emergence of neurotropic viruses.

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“…Cerebral organoids were also chosen because they develop immunocompetent astrocytes that are key players in neuroinvasive disease response [13]. While mid-brain organoids are standard for PD research, they omit the cerebral cortex that is integral to viral pathogenesis in the human CNS [14]. Thus, the goal of this study was to define differences in cerebral organoids derived from an individual with PD versus an individual without PD so that these model systems may be used to inform future studies of viral CNS infections.…”

Section: Introductionmentioning

confidence: 99%

Differences between Cerebral Organoids Derived from a non-PD and a Parkinson’s Patient: A Potential Vulnerability for Neuroinvasive Viruses

Schultz¹,

Jones²,

Xu³

et al. 2021

Preprint

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The development of 3D cerebral brain organoids which accurately resemble aspects of the human brain permits a more accurate characterization of physiological processes and neurological diseases. Cerebral organoids can be grown from stem cell lines with various genetic backgrounds allowing multiple neurodegenerative diseases to be modeled. While dysfunction in neurotransmission of patients with neurodegenerative diseases is expected, the impact of chronic neurodegeneration on the response to viral infection of the CNS is poorly understood. For instance, several mosquito-borne viruses like Dengue virus and West Nile Virus cause post-viral parkinsonism. How CNS infection might impact a host with inherent CNS dysfunction such as Parkinson’s Disease in poorly understood. This preliminary, observational study aimed to understand dysfunction in intrinsic and innate expression of a patient with a neurodegenerative disease and a non-affected individual in relation to potential viral infection in the CNS. Cerebral organoids were generated from human induced pluripotent stem cells with a normal genetic background or with idiopathic Parkinson’s Disease. After differentiation and maturation, organoid size, gene expression and immunofluorescence were evaluated to assess neurotransmission and innate immunity. While there was no significant difference in size of the organoids with a normal or Parkinson’s genetic background, gene expression studies identified multiple differences in innate immunity and neurotransmission. Immunofluorescence also identified differences in protein expression related to neurotransmission and innate immunity. Of note, organoids derived from a Parkinson’s patient exhibited endogenous up-regulation of dopamine and muscarinic acetylcholine receptors, GABA, glycine, and glutamate targets, and the majority of cytokines. This expression pattern suggests a chronic state of neuroexcitation and neuroinflammation in this population of organoids.

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Neurocognitive impacts of arbovirus infections

Cited by 40 publications

References 196 publications

Mayaro Virus Infects Human Brain Cells and Induces a Potent Antiviral Response in Human Astrocytes

Mayaro Virus Infects Human Brain Cells and Induces a Potent Antiviral Response in Human Astrocytes

Viral and Prion Infections Associated with Central Nervous System Syndromes in Brazil

Differences between Cerebral Organoids Derived from a non-PD and a Parkinson’s Patient: A Potential Vulnerability for Neuroinvasive Viruses

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