Aging-mediated lipid alterations in SARS-CoV-2 infection

• Grant number: 21/13711-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: December 01, 2022
• End date: May 31, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Sayuri Miyamoto
• Grantee: Rosangela Silva Santos
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/07937-8 - Redoxome - Redox Processes in Biomedicine, AP.CEPID
• Associated scholarship(s): 23/08462-5 - A deeper investigation in the lipid role for virus infections: phosphoinositides and oxylipins, BE.EP.DD

Abstract

Aging is a risk factor for the development and intensification of several diseases including viral infections such as that caused by Sars-Cov-2. Lipids are very important molecules. They act in inflammatory signaling and are also a source for viral replication. Lipids are necessary to produce double-layer membranes (DMVs) that will protect the virus from the host's immune system. Considering lipid alterations such as increased levels of plasma cholesterol and triacylglycerols (TG) in aging, in addition to obesity being a risk factor for the complication of COVID-19 and other viral diseases, the metabolic study of lipids becomes essential for the fights new waves of infections that may occur in the near future. This project proposes the study of lipid changes in aging in the following contexts: a) Evaluation of lipid changes and oxidative stress caused by aging in cell culture; b) Analysis viral load change in Sars-Cov-2 infection in control and senescent cells; c) Analysis of the action of enzymes involved in lipid metabolism in senescence and infection by Sars-Cov-2; d) Characterization of alterations these alterations using an in vivo model. For in vitro senescence induction, Vero CCL-81 and Calu-3 cell lines will be used. They are susceptible to Sars-Cov-2 infection. The impact of aging on the lipid and infection context will be evaluated in a Syrian hamster (Mesocricetus auratus) model. Lipidomics and oxylipidomics analysis will be performed by liquid chromatography coupled with LC/MS-MS mass spectrometry. The laboratory-adjusted oxylipidomics method allows the simultaneous identification of more than 120 oxidized lipids, including prostaglandins, thromboxanes and other eicosanoids important for the inflammatory response. The lipidomics analysis will allow the evaluation of lipid remodeling in the context of infection and aging. It is expected that the results of this project provide support for the lipid mechanisms involved in the evolution of the disease and viral replication in the context of aging. (AU)