Lipid droplets as viral carriers in adipocytes

• Grant number: 23/08666-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): October 31, 2023
• Effective date (End): October 30, 2024
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Mariana Kiomy Osako
• Grantee: Ana Beatriz do Anjos Souza
• Supervisor: Akira Ono
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: University of Michigan, United States
• Associated to the scholarship: 21/00218-2 - SARS-CoV-2 interactions with adipose tissue and implications for viral pathogenesis, BP.DR

Abstract

During the COVID-19 outbreak caused by the SARS-CoV-2 virus, a high prevalence of severe acute respiratory syndrome was observed in overweight and obese patients, who had higher rates of hospitalization and admission to intensive care units. Adipocytes, cells abundant in adipose tissue that express angiotensin-converting enzyme 2 (ACE2) receptors, have been identified as an extrapulmonary target for SARS-CoV-2 infection. In this study, we aim to elucidate the interactions between adipose tissue and SARS-CoV-2 and evaluate the role of lipid droplets as viral carriers transported via TNTs in adipocytes. We observed that viral replication increases as the time for differentiation of murine 3T3-L1 and human A41 cells into mature adipocytes increase. Interestingly, the Spike viral protein was found in compartments that appear to contact intracellular lipids in murine adipocyte cells, while SARS-CoV-2 double-stranded RNA was detected next to intracellular lipids in human adipocytes. In preliminary experiments in infected murine adipocytes, we identified the formation of cellular extensions containing lipid droplets and J2 tags, which are monoclonal antibodies targeting double-stranded RNA. Thus, we intend to investigate the role of these thin membranous structures as tunneling nanotubes (TNT) in intercellular viral infection and propagation to neighboring cells. Moreover, we aim to investigate the contribution of adipose tissue as a site for viral replication and production in mice under high-fat diet compared to normal chow-fed group. Our study will provide to deepen the knowledge about these interactions between SARS-CoV-2 and adipose tissue, as well as possible routes of viral dissemination, which are of paramount importance to understanding the replication and pathogenesis of the virus. (AU)