Genomewide CRISPR knockout screen identified PLAC8 as an essential factor for SADS-CoVs infection.

Zoonotic transmission of coronaviruses poses an ongoing threat to human populations. Endemic outbreaks of swine acute diarrhea syndrome coronavirus (SADS-CoV) have caused severe economic losses in the pig industry and have the potential to cause human outbreaks. Currently, there are no vaccines or specific antivirals against SADS-CoV, and our limited understanding of SADS-CoV host entry factors could hinder prompt responses to a potential human outbreak. Using a genomewide CRISPR knockout screen, we identified placenta-associated 8 protein (PLAC8) as an essential host factor for SADS-CoV infection. Knockout of PLAC8 abolished SADS-CoV infection, which was restored by complementing PLAC8 from multiple species, including human, rhesus macaques, mouse, pig, pangolin, and bat, suggesting a conserved infection pathway and susceptibility of SADS-CoV among mammals. Mechanistically, PLAC8 knockout does not affect viral entry; rather, knockout cells displayed a delay and reduction in viral subgenomic RNA expression. In a swine primary intestinal epithelial culture (IEC) infection model, differentiated cultures have high levels of PLAC8 expression and support SADS-CoV replication. In contrast, expanding IECs have low levels of PLAC8 expression and are resistant to SADS-CoV infection. PLAC8 expression patterns translate in vivo; the immunohistochemistry of swine ileal tissue revealed high levels of PLAC8 protein in neonatal compared to adult tissue, mirroring the known SADS-CoV pathogenesis in neonatal piglets. Overall, PLAC8 is an essential factor for SADS-CoV infection and may serve as a promising target for antiviral development for potential pandemic SADS-CoV.

Role of SARS-CoV-2 in Modifying Neurodegenerative Processes in Parkinson's Disease: A Narrative Review.

The COVID-19 pandemic, caused by SARS-CoV-2, continues to impact global health regarding both morbidity and mortality. Although SARS-CoV-2 primarily causes acute respiratory distress syndrome (ARDS), the virus interacts with and influences other organs and tissues, including blood vessel endothelium, heart, gastrointestinal tract, and brain. We are learning much about the pathophysiology of SARS-CoV-2 infection; however, we are just beginning to study and understand the long-term and chronic health consequences. Since the pandemic's beginning in late 2019, older adults, those with pre-existing illnesses, or both, have an increased risk of contracting COVID-19 and developing severe COVID-19. Furthermore, older adults are also more likely to develop the neurodegenerative disorder Parkinson's disease (PD), with advanced age as the most significant risk factor. Thus, does SARS-CoV-2 potentially influence, promote, or accelerate the development of PD in older adults? Our initial focus was aimed at understanding SARS-CoV-2 pathophysiology and the connection to neurodegenerative disorders. We then completed a literature review to assess the relationship between PD and COVID-19. We described potential molecular and cellular pathways that indicate dopaminergic neurons are susceptible, both directly and indirectly, to SARS-CoV-2 infection. We concluded that under certain pathological circumstances, in vulnerable persons-with-Parkinson's disease (PwP), SARS-CoV-2 acts as a neurodegenerative enhancer to potentially support the development or progression of PD and its related motor and non-motor symptoms.