lecture
Biomolecular Sciences

Global virus outbreaks: Interferons as 1st responders

Prof. Eleanor N. Fish
December 17, 2024
09:30 - 10:30

Viral infections pose a major threat to human health. Vaccines protect from specific

infections, yet newly emerging or pandemic viral strains that exhibit genetic drift or reassortment

of genes preclude immediate responses using a vaccine strategy. Moreover, for SARS CoV-2,

although current vaccines reduce severity of disease, they do not protect from re-infection,

resulting in persistent community transmission and outbreaks. The emergence of drug resistance

also mitigates against pathogen-specific antiviral drugs. A complementary strategy focusing on

the host not the pathogen is the basis for development of broad-spectrum antivirals.

Our immediate response to any and all virus infections is the immediate production of interferon

(IFN). Data reveal that the robustness of an IFN response to respiratory infections, determines

the outcome – an aggressive or mild infection. We provide evidence that an IFN response to viral

infection, and/or IFN treatment, induces an activated phenotype in target cells that results in an

antiviral state and an optimized innate immune response, regardless of the virus. We extended

these findings to examine the therapeutic potential of IFN treatment in hospitalized individuals

infected with SARS and showed that IFN treatment accelerated viral clearance and reduced lung

abnormalities. Similarly, using human lung explants, IFN treatment cleared infection against

H5N1 avian and pandemic H1N1 influenza strains. During the Ebola virus outbreak in West

Africa, we conducted a clinical study in Guinea and provided evidence of increased survival

associated with IFN treatment. At the start of the COVID-19 pandemic we undertook a clinical

study in Wuhan, China, providing evidence that early treatment with an inhaled IFN accelerated

viral clearance, reduced inflammation and also reduced lung abnormalities. Given that limiting

transmission is the solution to shutting down any outbreak, we next conducted a clinical trial to

determine whether IFN treatment of SARS CoV-2 exposed, but uninfected individuals, would

protect from infection. We provide evidence that prophylactic treatment with IFN limits

household transmission, being most effective when the infected case in the household has a high

viral burden.