SARS-CoV-2 ORF3a expression in brain disrupts the autophagy-lysosomal pathway, impairs sphingolipid homeostasis, and drives neuropathogenesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes injury to multiple organ systems, including the brain. SARS-CoV-2's neuropathological mechanisms may include systemic inflammation and hypoxia, as well as direct cell damage resulting from viral infections of neurons and glia. How the virus directly causes injury to brain cells, acutely and over the long term, is not well understood. In order to gain insight into this process, we studied the neuropathological effects of open reading frame 3a (ORF3a), a SARS-CoV-2 accessory protein that is a key pathological factor of the virus. Forced ORF3a brain expression in mice caused the rapid onset of neurological impairment, neurodegeneration, and neuroinflammation-key neuropathological features found in coronavirus disease (COVID-19, which is caused by SARS-CoV-2 infection). Furthermore, ORF3a expression blocked autophagy progression in the brain and caused the neuronal accumulation of α-synuclein and glycosphingolipids, all of which are linked to neurodegenerative disease. Studies with ORF3-expressing HeLa cells confirmed that ORF3a disrupted the autophagy-lysosomal pathway and blocked glycosphingolipid degradation, resulting in their accumulation. These findings indicate that, in the event of neuroinvasion by SARS-CoV-2, ORF3a expression in brain cells may drive neuropathogenesis and be an important mediator of both short- and long-term neurological manifestations of COVID-19.

Game-Theoretical Model of the Voluntary Use of Insect Repellents to Prevent Zika Fever.

Zika fever is an emerging mosquito-borne disease. While it often causes no or only mild symptoms that are similar to dengue fever, Zika virus can spread from a pregnant woman to her baby and cause severe birth defects. There is no specific treatment or vaccine, but the disease can be mitigated by using several control strategies, generally focusing on the reduction in mosquitoes or mosquito bites. In this paper, we model Zika virus transmission and incorporate a game-theoretical approach to study a repeated population game of DEET usage to prevent insect bites. We show that the optimal use effectively leads to disease elimination. This result is robust and not significantly dependent on the cost of the insect repellents.