Morphoproteomic Features of Pulmonary Influenza A (H1N1) with Therapeutic Implications: A Case Study

Objective. Influenza pandemic of the human lung was caused by the Influenza A (H1N1) over 100 years ago in 1918, but it recurred in pandemic fashion in 2009. Understanding the pathobiology of this infectious agent in the human lung could lead to adjuvant therapies that are relatively non-toxic and reduce the mortality of the human host. Overall, our objective was to apply morphoproteomics to pulmo-nary lung sections from an autopsied victim so that we may better define its biology from the perspective of its interaction with the host and provide options for therapeutic targets. Methods. Morphoproteomic analysis from a case study of this Influenza A (H1N1) pulmonary infection included immunohistochemical probes to detect the expressions of fatty acid synthase (FAS), CD163+ (M2 polarized monocytes/macro-phages), and programmed death-ligand 1 (PD-L1) expression as part of the host response to interaction with the Influenza A (H1N1) virus.Results. Representative sections of the Influenza A (H1N1) victim's lung showed: cytoplasmic expression of FAS in most of the sloughed and atypical alveolar pneumocytes;abundance of intra-alveolar and alveolar interstitial CD163+ macrophages/monocytes;and PD-L1 expres-sion on occasional macrophages, and focally on collections of alveolar pneumocytes and the alveolar inter-stitium.Conclusion. Morphoproteomics and microanatomical features coincide with the etiopathogenic features of pulmonary Influenza A (H1N1) infection and the host response. This plus data mining of the medical literature suggests that adjunctive, targeted therapy such as metformin and vitamin D3 could ad-dress the biology of Influenza A (H1N1) pneumonia, enhance the host immune response, and prevent its progression to a life-threatening, ventilator-dependent clinical situation.

Morphoproteomics and Etiopathogenic Features of Pulmonary COVID-19 with Therapeutic Implications: A Case Study.

OBJECTIVE: The COVID-19 pandemic has challenged the world economically and medically. Understanding and defining the biology of this specific coronavirus infection may lead to targeted therapies to lessen its virulence and expand the host resistance. This study's objective was to apply morphoproteomics to pulmonary lung sections from a forensic autopsy of an untreated COVID-19 victim, so that we may better define its biology from the perspective of its interaction with the host and provide options for therapeutic targets. DESIGN: Morphoproteomic analysis from a case study of this COVID-19 pulmonary infection included immunohistochemical probes to detect phosphorylated p-STAT3 (Tyr 705), as part of the interleukin (IL)-6 pathway; cyclooxygenase (COX)-2, CD8+ cytotoxic lymphocytes, Programmed Death (PD)-1 receptor+ lymphoid cells, CD56+ NK lymphoid cells, CD163+ (M2 polarized monocytes/macrophages), and programmed death-ligand 1 (PD-L1) expression as part of the host response to interaction with the COVID-19 virus. RESULTS: Representative sections of the COVID-19 victim's lung showed: nuclear expression of p-STAT3 (Tyr 705) in many of the alveolar pneumocytes and in occasional endothelial cells; COX-2 expression in the alveolar pneumocytes; a relative paucity of CD8+ cytotoxic lymphocytes; absence of CD56+ NK lymphoid cells; abundance of intra-alveolar and alveolar interstitial CD163+ macrophages/monocytes; PD-L1 expression on occasional macrophages, focally on collections of alveolar pneumocytes, and on cells in the alveolar interstitium; and rare PD-1+ lymphocytes in similar regions as CD8+ lymphocytes. CONCLUSION: Morphoproteomics and microanatomical features coincide with the etiopathogenic features of pulmonary coronavirus infection and the host response. This suggests that a targeted therapy could address the biology of COVID-19 pneumonia, enhance the host immune response and prevent its progression to a life-threatening, ventilator-dependent clinical situation.