Neurocognitive impacts of arbovirus infections

Abstract

Arthropod-borne viruses or arbovirus, are most commonly associated with acute infections, resulting on various symptoms ranging from mild fever to more severe disorders such as hemorrhagic fever. Moreover, some arboviral infections can be associated with important neuroinflammation that can trigger neurological disorders including encephalitis, paralysis, ophthalmological impairments, or developmental defects, which in some cases, can lead to long-term defects of the central nervous system (CNS). This is well illustrated in Zika virus-associated congenital brain malformations but also in West Nile virus-induced synaptic dysfunctions that can last well beyond infection and lead to cognitive deficits. Here, we summarize clinical and mechanistic data reporting on cognitive disturbances triggered by arboviral infections, which may highlight growing public health issues spanning the five continents.

Keywords: Arbovirus; Cognition; Long-term sequelae; Nervous system.

Fig. 1

The NVU and pathways of CNS viral entry through the BBB. a The NVU is formed by astrocyte end feet, perivascular microglia, neurons, as well as brain pericytes, which are embedded in the basement membrane and envelop the endothelial cells lining cerebral capillaries. b Description of possible mechanisms of CNS virus through the BBB. (1) Direct infection of endothelial cells that release viruses in the brain. (2) Infection of monocytes infiltrating the CNS by the Trojan horse mechanism. (3) Infection of endothelial cells that disrupt the BBB by the release of inflammatory mediators. (4) CNS cells participate in the disruption of CNS homeostasis by producing inflammatory molecules and allowing the recruitment of immune cells. Images created with BioRender.com and SMART- Servier Médical ART

Fig. 2

Elimination of synapses by microglia via the complement pathway. Activation of microglial complement receptors during arboviral infection triggers the phagocytosis of synapses. Complement components C1q, C4b/C2a, and the C3 fragment (C3b) tag synapses. Microglial cells bind C3b through their CR3 receptors and partially phagocyte tagged synapses, resulting in selective synapse elimination. Images created with SMART- Servier Médical ART