4 research outputs found
Viral afterlife: SARS-CoV-2 as a reservoir of immunomimetic peptides that reassemble into proinflammatory supramolecular complexes
It is unclear how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to the strong but ineffective inflammatory response that characterizes severe Coronavirus disease 2019 (COVID-19), with amplified immune activation in diverse cell types, including cells without angiotensin-converting enzyme 2 receptors necessary for infection. Proteolytic degradation of SARS-CoV-2 virions is a milestone in host viral clearance, but the impact of remnant viral peptide fragments from high viral loads is not known. Here, we examine the inflammatory capacity of fragmented viral components from the perspective of supramolecular self-organization in the infected host environment. Interestingly, a machine learning analysis to SARS-CoV-2 proteome reveals sequence motifs that mimic host antimicrobial peptides (xenoAMPs), especially highly cationic human cathelicidin LL-37 capable of augmenting inflammation. Such xenoAMPs are strongly enriched in SARS-CoV-2 relative to low-pathogenicity coronaviruses. Moreover, xenoAMPs from SARS-CoV-2 but not low-pathogenicity homologs assemble double-stranded RNA (dsRNA) into nanocrystalline complexes with lattice constants commensurate with the steric size of Toll-like receptor (TLR)-3 and therefore capable of multivalent binding. Such complexes amplify cytokine secretion in diverse uninfected cell types in culture (epithelial cells, endothelial cells, keratinocytes, monocytes, and macrophages), similar to cathelicidin’s role in rheumatoid arthritis and lupus. The induced transcriptome matches well with the global gene expression pattern in COVID-19, despite using <0.3% of the viral proteome. Delivery of these complexes to uninfected mice boosts plasma interleukin-6 and CXCL1 levels as observed in COVID-19 patients
Virulence Factors Associated with Enterococcus Faecalis Infective Endocarditis: A Mini Review
Interactions of Staphylococci with Osteoblasts and Phagocytes in the Pathogenesis of Implant-Associated Osteomyelitis
In spite of great advancements in the field of biomaterials and in surgical techniques, the implant of medical devices is still associated with a high risk of bacterial infection. Implant-associated osteomyelitis is a deep infection of bone around the implant. The continuous inflammatory destruction of bone tissues characterizes this serious bone infectious disease. Staphylococcus aureus and Staphylococcus epidermidis are the most prevalent etiologic agents of implant-associated infections, together with the emerging pathogen Staphylococcus lugdunensis. Various interactions between staphylococci, osteoblasts, and phagocytes occurring in the pen-prosthesis environment play a crucial role in the pathogenesis of implant-associated osteomyelitis. Here we focus on two main events: internalization of staphylococci into osteoblasts, and bacterial interactions with phagocytic cells