Roberto Cattaneo, Ph.D., studies enveloped ribonucleic acid (RNA) viruses that cause highly contagious diseases, including measles and coronavirus disease 2019 (COVID-19). These viruses cause disease by targeting specific cells — and, once inside these cells — interfering with innate immunity functions. Dr. Cattaneo's team characterizes different aspects of host cell-virus interactions, seeking to understand virulence and pathogenesis at the molecular level.
The National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and other national and international granting agencies fund Dr. Cattaneo's research.
- Virus tropism and pathogenesis
- Cell entry and membrane fusion
- Antagonism of innate immunity
- Genome variability and tissue adaptation
- Viral vectors for vaccination and oncolysis
Key virus-cell interactions occur at cell entry, when viruses contact specific receptors. Dr. Cattaneo’s team discovered why measles virus, which uses a protein (SLAMF1) expressed on immune cells as primary receptor to spread systemically in the host, is extremely contagious: It uses a protein (nectin-4) expressed in the trachea to exit from the host at a location leading to efficient aerosolization through coughing and sneezing. This discovery established the concept of “host-exit receptor” (Nature, PMID 22048310).
Another focus area is the activation and execution of membrane fusion. Dr. Cattaneo’s team has made numerous contributions to the understanding of how the membrane fusion apparatus of measles and other viruses is activated, and of the sequence of events that leads to membrane fusion (J. Biol. Chem., PMID 31949044). The team is now focusing also on the mechanisms of activation, and execution of membrane fusion, by the SARS-CoV-2 envelope.
A key question is how RNA viruses adapt to different organs of their hosts. Dr. Cattaneo’s team has shown that in its two natural cellular environments, lymphocytes and epithelial cells, distinct populations of measles virus genomes exist, and suboptimal variants in one environment constitute a reservoir for adaptation to the other (PLoS Pathogens, PMID 30768648). This cyclical adaptation mechanism leads to tissue-specific expression of an innate immunity antagonist, and the team is now assessing whether similar adaptive processes occur also in SARS-CoV-2 infections.
Significance to patient care
Dr. Cattaneo's team addresses two respiratory viruses that are significant public health threats. Measles virus vaccination program interruptions through the emergence of SARS-CoV-2 are setting back the measles eradication program. Seeking to understand the determinants of virulence and pathogenesis at the molecular level remains highly important for both infections.
New frontiers of virology include the generation of virus-derived vectors to eliminate cancer cells and deliver therapeutic genes to specific cells and organs. Dr. Cattaneo's basic research into measles virus has laid the foundations for the development of measles virus-based clinical trials of glioma, myeloma and ovarian cancer currently ongoing at Mayo Clinic.
More information about Dr. Cattaneo:
- Vice-chair for Education, Department of Molecular Medicine, 2014-present
- Director, Virology and Gene Therapy Graduate Track, Mayo Graduate School of Biomedical Sciences, 2004-2015
- Chair, Education Committee (2007-2009); Chair, Infectious Diseases and Vaccines Committee (2009-2011); Member, Board of Directors (2010-2013) — American Society of Gene & Cell Therapy
- START Career Development Award, Swiss National Science Foundation, 1991-1998