Trained immunity involving HERV-K102 activation in foamy macrophages may promote recovery from COVID-19 providing a new innate immunity vaccination paradigm against pandemic RNA viruses
Abstract for an invited paper: A work in progress. July 7, 2023.
Figure 1. HERV-K102 particle production in monocytes/macrophages generates pro-inflammatory M1-like lipid body negative foamy macrophages (LB-FMs) that have a lacy/foamy appearance due to particles budding into vacuoles. This generates trained innate immunity.
ABSTRACT
SARS-CoV-2 spike-specific IgG antibodies which are a component of adaptive immunity and stimulated by the second dose of the COVID-19 vaccines, have been unequivocally proven to cause progression of COVID-19 disease during natural infection. This is due to antibody dependent enhancement (ADE) of SARS-CoV-2 infection into macrophages which circumvents critical innate immunity. Indeed, early interferon responses and monocyte-macrophage innate immunity mechanisms as favored by optimal vitamin D levels, are well established correlates of protection against COVID-19. Trained immunity (TI) refers to the memory response of innate immunity which involves metabolic and epigenetic reprogramming that allows for heightened subsequent beta interferon and host inflammatory responses in macrophages upon rechallenge. Human endogenous retrovirus K102 (HERV-K102) is a protector, replication-competent foamy retrovirus that induces foam cell formation in macrophages due to its particles budding into vacuoles. The mevalonate (cholesterol) pathway and foam cell formation in macrophages comprise TI, meaning HERV-K102 particle production and foam cell formation are central to macrophage TI. Furthermore, the promotor and enhancer regions of HERV-K102 indicate responsiveness to beta interferons, vitamin D, glucocorticosteroids and other hormones, as well as IRF1, STATs, and NFKB1 transcription factors involved in proinflammatory M1-like macrophage differentiation. Here it is proposed that HERV-K102 particle production in lipid-body negative (M1-like and pro-inflammatory) foamy macrophages including constitutive expression in sebocytes of sebaceous glands of the mucosa, may be the elusive component of TI critical to the early clearance of SARS-CoV-2 and recovery from COVID-19. The various mechanisms by which the HERV-K102 trained immunity system may protect against COVID-19 and evidence for the loss of HERV-K102 activity with COVID-19 severity, are provided. This review posits that enhancement of HERV-K102 particle production and lytic release from foamy macrophages constitutes a new TI paradigm for pandemic preparedness vaccinology but is also useful for prevention and early treatment strategies.
Line 18 of abstract- "promoter" or "promotor"?
I hope that you can achieve publication rather than experiencing "cancellation" (as opposed to retraction) as Dr. McCullough did with his review.