Unraveling the long-term impact of an acute respiratory virus infection

Abstract
Respiratory viruses including the human parainfluenza viruses (hPIVs) are a constant burden to human health, with morbidity and mortality frequently increased after the acute phase of the infection. Although is proven that respiratory viruses can persist in vitro, the mechanisms of virus or viral products persistence, their sources, and their impact on chronic respiratory diseases in vivo are unknown. Here, we used Sendai virus (SeV) to model hPIV infection in mice and test whether virus persistence associates with the development of chronic lung disease. Following SeV infection, virus products were detected in lung macrophages, type 2 innate lymphoid cells (ILC2s) and dendritic cells for several weeks after the infectious virus was cleared. Cells containing viral protein showed strong upregulation of antiviral and type 2 inflammation-related genes that associate with the development of chronic post-viral lung diseases, including asthma. Lineage tracing of infected cells or cells derived from infected cells suggests that distinct functional groups of cells contribute to the chronic pathology. Importantly, targeted ablation of infected cells or those derived from infected cells significantly ameliorated chronic lung disease. Overall, we identified persistent infection of innate immune cells as a critical factor in the progression from acute to chronic post viral respiratory disease.

About the Speaker
Dr. López is the Theodore and Bertha Bryan Professor of Environmental Medicine and BJC Investigator at the Department of Molecular Microbiology at Washington University in St. Louis, School of Medicine. Dr. López came to the USA in 1996 after graduating as a Biochemist and obtaining a MS from the Universidad Católica de Chile. She obtained a Ph.D. from the Mount Sinai School of Medicine in NY (now Icahn School of Medicine at Mount Sinai) working in the laboratory of Thomas Moran (1997-2002) and continued in the same laboratory for postdoctoral and junior faculty positions. At the Moran lab she investigated how the immune response is initiated in response to infection with influenza and parainfluenza viruses and studied the impact of type I interferons on the immune response to viral infection. Dr. López joined the University of Pennsylvania in 2010 as an Assistant Professor and was promoted to tenured Associate Professor in 2016. She relocated to the Washington University in St Louis in June of 2020.

Dr. López’ laboratory seeks to understand how respiratory viruses interact with their host with a focus on identifying viral and cellular factors that drive the development of antiviral immune responses able to control virus replication and dissemination. Work from the López Lab revealed that replication defective forms of viral genomes that accumulate naturally during infections are fundamental components of RNA viruses and play a critical role in determining the outcome of infections. In addition, the López laboratory seeks to discover determinants of acute and chronic respiratory virus pathogenesis that could be targeted to ameliorate the burden of viral diseases. In this area, the laboratory has contributed to the understanding of how viruses persist in the respiratory tract and the impact of persistent respiratory viruses on the development of chronic lung pathologies. Research in the López laboratory has strong virology and immunology components and uses multiple strategies to gain mechanistic understanding of the processes that drive antiviral immunity, as well as those contributing to viral pathogenesis.

Dr. López is a Fellow of the American Society for Microbiology and a 2018-2019 US Fulbright Scholar. She has served in the editorial board of multiple journals and currently is editor for mBio and Science Advances. Dr. López has served in various national and international grant review study sections and is currently member of the Advisory Committee for the Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Disease program. She served as member of the Committee on the Status of Women (2012-2015) and the Program Committee (2017-2020) for the American Association of Immunologists, and was a member of the Council on Microbial Sciences (2017-2020) for the American Society for Microbiology. Dr. López is a Fellow of the Professional Mentoring Skills Enhancing Diversity Program funded by the NIH-National Research Mentoring Network.

Contact

Moriah Szpara
mls164@psu.edu