Abstract Text: Respiratory viruses are the leading cause of acute lower tract respiratory infection, mainly in infants, elderly and immunocompromised individuals, causing high morbidity and mortality rates. The most important of this kind of virus is the respiratory syncytial virus (hRSV), which can cause severe clinical pathologies, including bronchiolitis and pneumonia. However, increasing evidence shows this virus's ability to cause neurological alterations, such as seizures, encephalitis, and encephalopathy. Reports have been shown to detect hRSV RNA and pro-inflammatory molecules in cerebrospinal fluid from patients with neurological signs, supporting the notion of neuroinvasion and neuroinflammation caused by hRSV. Previous data has shown the detection of viral RNA and proteins in the brain of infected mice. In this research, we show that the viral infection alters the blood-brain barrier permeability, altering the tight junctions' expression and allowing the immune cells to infiltrate and increase pro-inflammatory molecules during and after the infection. Moreover, hRSV can infect astrocytes, microglia, neurons, and endothelial cells. Also, the alteration in the glutamate receptors' expression could cause behavioral impairment observed in mice after the hRSV clearance. The brain hRSV-infected cells such as astrocytes, neurons, and endothelial cells can secrete pro-inflammatory cytokines that could alter the neurological synapse's normal establishment and contribute to the long sequels observed in the mice model. . Our work provides new insight into the effect of hRSV on the central nervous system and underscores the need to further understand how respiratory virus can damage brain function in humans.
