Pneumoviruses can impair the central nervous system by different mechanisms

Abstract Pneumoviruses such as the respiratory syncytial virus (hRSV) and the human metapneumovirus (hMPV) are the leading cause of acute lower tract respiratory infection, mainly in infants, elderly and immunocompromised individuals, causing high morbidity and mortality rates. However, these viruses can cause neurological alterations, such as encephalitis and encephalopathy. Viral RNA and pro-inflammatory molecules have been found in patients with neurological signs, supporting the notion of neuroinvasion and/or neuroinflammation caused by hRSV and hMPV. Therefore, this work seeks to evaluate the effects of these viruses on the brain. Accordingly, mice were infected with either hRSV or hMPV or treated with non-infectious controls (mock). Despite detecting viral load in the lungs of hMPV-infected mice, no viral load was detected in their brains, as it was shown for hRSV. However, pro-inflammatory cytokines such as IL-6 and IFN-g were increased only in the sera of hMPV-infected mice. Also, we observed differential patterns in the increase of cytokines in the brain of hRSV or hMPV-infected mice, including IL-6, TNF-a, and IL-4. Moreover, increased blood-brain barrier permeability was observed in mice infected with both viruses. Additionally, after several weeks post-infection, a Marble Burying (MB) test was performed, and we observed an impaired cognitive performance in mice infected with both viruses. All these results suggest that infection with these pneumoviruses can cause long-term behavioral impairment in mice. Our work provides new insight into the effect of hRSV and hMPV on the central nervous system and underscores the need to further understand how respiratory virus can damage brain function in humans. This work was supported by ANID/FONDECYT grants #11221280; #1190830, ANID scholarship # 21210662, the Millennium Institute on Immunology and Immunotherapy ACE 210015, ICN09_016 / ICN 2021_045; former P09/016-F.