17 Apr 2024
Exploring the ripple effects of co-infections: how unrelated viruses shape immune responses to influenza
Research typically focuses on studying the immune response to a single pathogen infection, but not much is known on how multiple infections, either consecutive or simultaneous, affect anti-viral immunity.
A study from the Doherty Institute published in Nature Communications, delved into this very question: what is the impact of prior infection with an unrelated virus on the body's response to influenza?
Using pre-clinical models, researchers investigated consecutive infections with two distinct viruses: influenza A (IAV) and Semliki Forest virus (SFV), a mosquito-borne arbovirus which affects the central nervous system, particularly the brain.
University of Melbourne Isabelle Foo, PhD candidate in the Kedzierska Lab at the Doherty Institute and first author of the paper, explained that the sequence of infection matters.
“When SFV infection occurred first, it altered the body's immune response to IAV, resulting in worsened flu symptoms and poor health outcomes,” said Ms Foo.
Indeed, the team discovered that infection with SFV followed by infection with IAV leads to severe damage to the lungs, increased inflammation and prolonged flu virus replication. They also made an unexpected discovery.
“We found that when SFV infects the body first and IAV after, IAV-specific immune cells, usually found in the lungs, unexpectedly travelled to the brain. This really puzzled us!” she added.
University of Melbourne’s Dr Lukasz Kedzierski, Senior Research Fellow at the Doherty Institute and co-senior author of the study, said these findings have significant implications for public health, especially considering that influenza viruses and encephalitic viruses often co-occur globally.
“People are exposed to multiple pathogens at any given time, but immune responses to co-infections with different types of pathogens remain largely understudied, despite how commonly they occur,” said Dr Kedzierski.
“Many cases of infections with arboviruses are asymptomatic and not typically considered a risk during an influenza virus infection. However, our study shows that a previous infection with arboviruses can significantly alter the body's response to influenza, potentially leading to more severe respiratory illnesses or weakening long-term immunity.”
University of Melbourne’s Professor Katherine Kedzierska, Head of the Human T cell Laboratory at the Doherty Institute and co-senior author of the paper, emphasised the importance of considering co-infections when studying immune responses and designing treatments.
“Understanding how prior infections with unrelated viruses can affect the immune response to influenza may help predict and manage the severity of respiratory illnesses and design effective medical interventions,” said Professor Kedzierska.
“Our research offers crucial insights into developing more targeted and effective treatment and vaccine strategies to combat infectious diseases.
“This study represents a notable advancement in the field of immunology and holds significant implications for healthcare professionals globally.”
Peer review: Foo I, et al. Prior infection with unrelated neurotropic virus exacerbates influenza disease and impairs lung T cell responses. Nature Communications (2024). https://doi.org/10.1038/s41467-024-46822-7
Funding: University of Melbourne and the NHMRC
Featured article on Nature Communications Editors' Highlights page: https://www.nature.com/collections/jedgcgeija