Active Infection & Immunity Genetics & Molecular Biology

Virus cross-species transmission. Defining the immunological barriers to viral emergence

In plain English

AI plain-English summary

Every day, humans inhale viruses from birds, pigs, and other animals—but most never cause a pandemic. This programme asks why some animal viruses fail to spread in people, while others like influenza H5N1 succeed. The problem is that current pandemic surveillance focuses on spotting new viruses after they have already infected humans. What is missing is a clear picture of the immune barriers that stop most animal viruses before they start. Without that knowledge, public health agencies cannot predict which circulating animal viruses pose the greatest threat. The researchers will tackle three specific questions. First, they will identify which antiviral genes—called interferon-stimulated genes—block respiratory viruses in human cells. Second, they will pinpoint the exact viral proteins and amino acid residues that allow avian influenza to jump into humans. Third, they will map the antibody landscape in humans and key animal species to understand how pre-existing immunity might constrain viral emergence. If successful, the programme will deliver actionable data for risk assessment. Health agencies could use these findings to rank animal viruses by their zoonotic potential, prioritise surveillance, and design vaccines or treatments against the most dangerous candidates before they cause outbreaks. This is fundamental science with a direct pipeline to pandemic preparedness.

View original technical description
Humans are constantly exposed to a variety of animal viruses. Understanding why most of these viruses fail to spillover and thrive in human populations is crucial to devise optimal strategies to manage viral emergence. Our programme aims to understand diverse immunological barriers to virus cross-species transmission. Our hypothesis is that the genetic and immunological variability of each individual or species helps define susceptibility or resistance to virus cross-species transmission. Our first aim is to identify those genes that are activated immediately after virus infection (known as interferon-stimulated genes, ISGs) and block respiratory viruses. Our second aim is to create a risk assessment framework to identify those specific viral proteins (and specific amino acid residues within the proteins) that favour the spillover of avian influenza viruses into the human population. The third and last aim of the programme is to understand the antibody landscape in humans and selected animal species, in order to estimate the impact of cross-neutralising antibodies and, at the population level, cross-immunity on constraining viral emergence. At the end of this programme, we will be able to translate our discoveries by delivering actionable data that can support the risk assessment of the zoonotic potential of viruses.

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Researchers

Daniel Streicker (Co-Investigator)Massimo Palmarini (Principal Investigator)Pablo Murcia (Co-Investigator)Sam Wilson (Co-Investigator)Suzannah Rihn (Co-Investigator)

Related Research

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Innate Immunity and Host Species Barriers
Three species viral zoonotic infections - a systems virology analysis
Antiviral restriction factors: Understanding determinants of host range and barriers to species-jumping in livestock viral disease
Viral entry at the human-animal interface; dissecting the pan-tropic nature of zoonotic viruses.
Identification of interferon stimulated genes that restrict cross-species transmission of influenza A virus.

Original classification

Intramural

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