Cell Biology of Viral Infection
Mission
The main interest of the Cell Biology of Viral Infection Research Group is to understand how evolving viruses replicate inside their different hosts (humans and other animals), and the type of response that the host mounts to defend against the challenge. In particular, we seek to find the virus' Achilles heels that may become novel antiviral strategies. Currently, we investigate how viruses utilize material properties to accomplish specific aspects of their lifecycle.
Importance
Viruses cause disease in all forms of life, including humans and animals. Influenza A virus is one of the major causes of acute contagious respiratory disease in humans, leading to seasonal epidemics and sporadic deadly pandemics. Despite tight surveillance of circulating strains worldwide, and the implementation of yearly vaccination schemes, the pathogen is responsible for high mortality, morbidity and economic damage.
Main Research Interests
The main interest of the Cell Biology of Viral Infection Research Group is to understand viral-host interactions at the cell biology level using an integrative approach combining in vitro, ex-vivo, and in vivo model systems of infection to provide not only mechanistic insight but also to validate their physiological relevance at the level of the organism.
In particular, we aim to understand the interplay of viruses and cells at each step of the replication cycle, identify key host factors and pathways essential for viral replication, as well as virulence factors impacting the disease of evolving viruses. We use mainly influenza A virus as viral model, comprehending how generalized our findings are for infection using many circulating viral strains and also influenza B virus.
Lung tissue from a mouse infected with the influenza A/Puerto Rico/34/8 virus on the second day of infection, showing the host cells in blue (marking the nucleus) and the cells where the virus is replicating in red (marking the viral protein nucleoprotein).
Our most recent line of research, merges virology and soft matter science, exploring concepts of liquid-liquid phase separation (LLPS) in viral infection. We have two overarching goals: 1) to explain how influenza epidemic and pandemic segmented genomes assemble; and 2) to dissect how viral infection uses and/or changes cellular biomolecular condensates, including those arising in response to infection and stress.
Human lung epithelial cells (A549) infected with influenza A/Puerto Rico/34/8 virus under normal conditions (left panel) or under conditions in which they do not form viral inclusions (marked in yellow, right panel) due to lack of expression of the cellular protein Rab11A (marked in magenta). The endoplasmic reticulum is highlighted in blue.
Human lung epithelial cells (A549) infected with influenza A/Puerto Rico/34/8 virus under conditions in which viral inclusions (marked in yellow) and the cellular protein Rab11A (marked in magenta) form rigid rather than liquid structures. The endoplasmic reticulum is highlighted in blue. This strategy could lead to the development of antivirals.
Since SARS-CoV-2 pandemics, we developed alternative methods of identifying SARS-CoV-2 infected people, especially in children, and understanding how viral SARS-CoV-2 variants escape neutralizing antibodies upon natural infection and vaccination. In sum, our laboratory has been unique in providing key insights on viral replication and how viral infection impacts the immune response and physiology of the infected organism.
Tools and models
The laboratory uses two systems as eukaryotic models: the mouse model and cultured cells (primary, transformed and immortalized). We study influenza A viruses mostly. Our model virus of choice, due to the availability of reagents and a powerful reverse genetics system, is influenza A/Puerto Rico/8/34. However, we have a portfolio of different influenza A viruses to test whether our findings are generally applicable to influenza A infection. Other types of viruses that we study include influenza B viruses, herpes simplex-1 and vaccinia virus, but the latter 2 are used only for exploring particular aspects of the biology of the cell. Other viruses that we study in the laboratory include SARS-CoV-2, herpes simplex virus 1, vaccinia, Zika, and Dengue which are studied in parallel in specific projects that focus on particular cellular structures such as cilia and the search for antivirals.
The laboratory uses a diversified set of multidisciplinary approaches to molecular biology, biochemistry, and microscopy, including live cell imaging, to unravel influenza A interactions with its host.
Human lung epithelial cells (A549) infected with filamentous influenza A virus (left) or not infected (right).
Funding
- an ERC consolidator Grant (LOFlu, ref 101001521) from 2021 to 2026. The EU-funded LOFlu project will investigate the host-pathogen interactions in influenza A virus (IAV) infection. Particular emphasis will be given to viral inclusions with liquid properties that form during viral assembly and constitute a key step in the virus life cycle.
- a La Caixa Grant (BioPlaTTAR) from 2022-2025. This builds BioPlaTTAR, an integrated platform for biopharmaceutical development, to quickly and efficiently respond to viral outbreaks - from lead generation to pre-clinical translation.
- Several FCT grants that cover the salary of our PhD students.
Important external links