Viral infections are a leading cause of morbidity and mortality globally, and they are major threats to global health systems. A recent analysis of global disease burden estimates attributed ~178 million disability-adjusted life years to viral infections among a group of 85 pathogens in 2019 alone1. In this issue, we explore viral pathogen emergence, evolution and spread, how their continued adaptation affects global health, and how advances in molecular epidemiology and viral surveillance, pandemic preparedness and control strengthen our ability to respond to ongoing and emerging threats.

The emergence, evolution and spread of viral pathogens are being influenced by global change. Climate change, land-use change, urbanization and increased global travel and trade are affecting the ecosystems in which viruses circulate and are providing new opportunities for zoonotic spillover, transmission and adaptation. For instance, the geographical expansion of mosquito-borne viruses such as dengue virus and chikungunya virus has been linked to climate change and urbanization2. The recent international spread of mpox to 115 countries where the virus had not been reported before highlights how interconnected human populations are and how this can quickly facilitate viral dissemination worldwide3. The emergence of SARS-CoV-2 in late 2019 also showed how a new virus can rapidly spread through a highly connected world. Since then, its continued evolution with the emergence of numerous variants and subvariants with differences in transmissibility and immune escape capabilities has highlighted the need for constant surveillance and the need to adapt our approaches to viral control.

SARS-CoV-2 variants are responsible for more than 775 million reported infections and more than 7 million deaths worldwide to date4, and they are an example of the remarkable evolutionary plasticity of viruses. In their Review, Uraki et al. explore the origins and evolution of SARS-CoV-2 variants, and they examine differences in variant biology, clinical characteristics and control. They also provide perspectives on pioneering vaccine strategies that could address the challenges posed by emerging variants and waning immunity.

Understanding why new viral threats emerge and detecting them early are crucial if they are to be prevented and controlled. In their Review, Sikkema and Koopmans examine the drivers of viral pathogen emergence, including climate change, land-use change, urbanization and global mobility, and how this knowledge could inform prevention and the development of a One Health early warning system that integrates this understanding into viral surveillance.

Since their detection in 1996, highly pathogenic avian influenza H5 viruses of the A/Goose/Guangdong/1/1996 lineage have posed a persistent threat to human and veterinary health. They have frequently caused large-scale outbreaks in domestic poultry and wild birds, leading to huge mortality and economic losses for farmers, with occasional spillover infections in humans with fatal outcomes. More recently, it has become evident that these viruses infect a much broader host range than previously thought; they have been identified in more than 80 mammalian species, including cattle, and during recent outbreaks on dairy farms in North America, the virus was found in milk and milking equipment, pointing to an unexpected transmission route via udders5,6. In their Review, Fouchier and colleagues explore the evolution, spread and impact of highly pathogenic avian influenza H5 viruses and their adaptation to mammals. They also discuss a One Health approach to managing viral threats to human and animal health.

The effective detection of new viral threats requires diagnostic and surveillance approaches that can identify viruses rapidly even without any prior knowledge of the pathogen, and viral metagenomics offers the potential to uncover novel and unknown pathogens. In their Review, Morfopoulou, Breuer and colleagues outline the laboratory and bioinformatics methods of clinical viral metagenomics and how they can be used as tools for viral pathogen diagnosis, surveillance and pathogen discovery. The authors also highlight how automation and the use of artificial intelligence-driven data analysis could support wider implementation of metagenomics in the clinic. In this issue’s Genome Watch, King and Mellor also explore studies that show how metagenomics is being applied to investigate viral diversity and track emerging zoonotic disease threats from wildlife.

Viral genomics is also crucial for understanding and controlling long-established viral pathogens such as HIV-1. The extraordinary diversity of HIV-1 and its constant evolution in response to host and treatment selection pressures means that phylogenetics and molecular epidemiology have become useful tools for tracking transmission patterns, monitoring antiretroviral resistance and evaluating the impact of public health initiatives. In their Review, Günthard et al. describe how phylogenetics and molecular evolution are being applied to understand and curb the HIV-1 pandemic, and they highlight the need to expand access to sequencing technologies in low- and middle-income countries where the burden of HIV-1 is highest.

“Sustained investment in global surveillance and early warning systems, and equitable access to interventions, are essential to tackle ongoing viral outbreaks and to respond to future threats”

All of the articles in this Focus issue serve as a reminder that viruses are persistent and evolving threats. Sustained investment in global surveillance and early warning systems, and equitable access to interventions, are essential to tackle ongoing viral outbreaks and to respond to future threats. As stated by Tedros Adhanom Ghebreyesus, WHO Director-General, the recent WHO Pandemic Agreement shows “that in our divided world – nations can still work together to find common ground and a shared response to shared threats”7. Nature Reviews Microbiology will continue to shine a strong light on the research that advances our ability to understand and respond to these threats.