Cell Biology of Viral Infection

Maria João Amorim

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. Development of novel ways to control infection is therefore necessary. The elucidation of host factors contributing to a productive infection, as well as host pathways that are able to regulate it can lead to novel therapies.

The Cell Biology of Viral Infection Lab is interested in understanding the interactions between influenza A virus and the infected host at different levels. By identifying the host machinery necessary to sustain viral infection we seek to understand the viral lifecycle and unravel key aspects of the biology of the cell.

Our goal is to explain if the viral usage of a certain pathway induces alterations to its normal functioning and to the overall morphology of the cell. By studying the host response to viral challenge, we seek to unravel host innate immune responses and ways to control viral infection.




Influenza A virus constitutes a serious health problem being responsible for a quarter to half a million deaths annually, depending on the pathogenicity of the circulating strain, prior immunity, and effectiveness of the administered vaccine.

Pathogenesis determinants include the intrinsic properties of IAV strains, and their interplay with host defence mechanisms. The Amorim lab found a specific interaction between influenza A virus and the complement system. With renewed interest caused by implementation of successful complement-targeting therapies, the complement is not just a pathogen killer, but a key player in immunity. It bridges innate and adaptive responses, and orchestrates the intensity of immunological and inflammatory processes by communicating with immune cells. Interactions are beginning to be fully appreciated, and their identification is crucial, as excess complement activation is associated with severe outcomes in many infections. In addition, the complement must be selective enough to avoid mounting a potent attack against the host. The self-targeting deleterious effects of complement are avoided via a series of so called regulators of complement activation (RCA). Our goal is to understand the role of these RCAs in influenza A virus infection, contributing to better define how complement communicates with other biological systems.

Mitochondria were originally described as the powerhouse of the cell, but their importance expanded as their role in controlling death processes was discovered.

More recently, these organelles also emerged as central players in innate immune processes, in particular interferon responses, which constitute the first line of defense against viruses. It is therefore not surprising that viruses interfere with mitochondrial pathways. Mitochondria functions are intimately related to dynamic changes in their morphology and distribution within the cell. Therefore, the characterization of these two parameters during influenza A virus infection is being investigated as well as the cellular processes leading to identified alterations. In addition, the Amorim lab found an interaction between mitochondria, the recycling endosome and influenza A virus that is currently being investigated.

Viral assembly is a fascinating molecular biology process. Once a virus enters a cell and replicates, it needs to form new virions that are composed of viral genome and specific proteins. These components, synthesized in distinct cellular organelles, are therefore required to meet at specific cellular locations to form a supra-molecular complex. In the case of influenza A virus this process is particularly challenging because the viral genome is segmented, formed by eight independent RNA units. The formation of the genomic complex and the biological processes facilitating the assembly of viral genome are ill-defined. Formation of IAV genomic complex is a complex selective process, as virions do not usually package more than eight segments and each segment generally occurs once per virion. Although it is well established that viral assembly takes place at the plasma membrane, it is still unclear where the genomic complex is formed. Recently, we demonstrated that influenza A virus (IAV) establishes viral inclusions that favor infection. We propose that viral inclusions constitute dedicated sites for the assembly of influenza genomes. Two interesting concepts have arisen from our work:

  1. viral inclusions have liquid properties;
  2. there is a close association between viral inclusions and the endoplasmic reticulum.

The lab is currently investigating these topics and exploring their potential as antiviral targets.


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