The evolutionary drivers and correlates of viral host jumps
Most emerging and re-emerging infectious diseases stem from viruses that naturally circulate in non-human vertebrates. When these viruses cross over into humans, they can cause disease outbreaks, epidemics and pandemics. While zoonotic host jumps have been extensively studied from an ecological perspective, little attention has gone into characterizing the evolutionary drivers and correlates underlying these events. To address this gap, we harnessed the entirety of publicly available viral genomic data, employing a comprehensive suite of network and phylogenetic analyses to investigate the evolutionary mechanisms underpinning recent viral host jumps. Surprisingly, we find that humans are as much a source as a sink for viral spillover events, insofar as we infer more viral host jumps from humans to other animals than from animals to humans. Moreover, we demonstrate heightened evolution in viral lineages that involve putative host jumps. We further observe that the extent of adaptation associated with a host jump is lower for viruses with broader host ranges. Finally, we show that the genomic targets of natural selection associated with host jumps vary across different viral families, with either structural or auxiliary genes being the prime targets of selection. Collectively, our results illuminate some of the evolutionary drivers underlying viral host jumps that may contribute to mitigating viral threats across species boundaries.
The majority of emerging and re-emerging infectious diseases in humans are caused by viruses that have jumped from wild and domestic animal populations into humans (that is, zoonoses)1. Zoonotic viruses have caused countless disease outbreaks ranging from isolated cases to pandemics and have taken a major toll on human health throughout history. There is a pressing need to develop better approaches to pre-empt the emergence of viral infectious diseases and mitigate their effects. As such, there is an immense interest in understanding the correlates and mechanisms of zoonotic host jumps1,2,3,4,5,6,7,8,9,10.
Most studies thus far have primarily investigated the ecological and phenotypic risk factors contributing to viral host range through the use of host–virus association databases constructed mainly on the basis of systematic literature reviews and online compendiums, including VIRION11 and CLOVER12. For example, ‘generalist’ viruses that can infect a broader range of hosts have typically been shown to be associated with greater zoonotic potential2,3,5. In addition, factors such as increasing human population density1, alterations in human-related land use4, ability to replicate in the cytoplasm or being vector-borne3 are positively associated with zoonotic risk. However, despite global efforts to understand how viral infectious diseases emerge as a result of host jumps, our current understanding remains insufficient to effectively predict, prevent and manage imminent and future infectious disease threats. This may partly stem from the lack of integration of genomics into these ecological and phenotypic analyses.
One challenge for predicting viral disease emergence is that only a small fraction of the viral diversity circulating in wild and domestic vertebrates has been characterized so far. Due to resource and logistical constraints, surveillance studies of novel pathogens in animals often have sparse geographical and/or temporal coverage13,14 and focus on selected host and pathogen taxa. Further, many of these studies do not perform downstream characterization of the novel viruses recovered and may lack sensitivity due to the use of PCR pre-screening to prioritize samples for sequencing15. As such, our knowledge of which viruses can, or are likely to emerge and in which settings, is poor. In addition, while genomic analyses are important for investigating the drivers of viral host jumps16, most studies do not incorporate genomic data into their analyses. Those that did have mostly focused on measures of host2 or viral3 diversity as predictors of zoonotic risk. As such, despite the limited characterization of global viral diversity thus far, existing genomic databases remain a rich, largely untapped resource to better understand the evolutionary processes surrounding viral host jumps.
Further, humans are just one node in a large and complex network of hosts in which viruses are endlessly exchanged, with viral zoonoses representing probably only rare outcomes of this wider ecological network. While research efforts have rightfully focused on zoonoses, viral host jumps between non-human animals remain relatively understudied. Another important process that has received less attention is human-to-animal (that is, anthroponotic) spillover, which may impede biodiversity conservation efforts and could also negatively impact food security. For example, human-sourced metapneumovirus has caused fatal respiratory outbreaks in captive chimpanzees17. Anthroponotic events may also lead to the establishment of wild animal reservoirs that may reseed infections in the human population, potentially following the acquisition of animal-specific adaptations that could increase the transmissibility or pathogenicity of a virus in humans13. Uncovering the broader evolutionary processes surrounding host jumps across vertebrate species may therefore enhance our ability to pre-empt and mitigate the effects of infectious diseases on both human and animal health.
A major challenge for understanding macroevolutionary processes through large-scale genomic analyses is the traditional reliance on physical and biological properties of viruses to define viral taxa, which is largely a vestige of the pre-genomic era18. As a result, taxon names may not always accurately reflect the evolutionary relatedness of viruses, precluding robust comparative analyses involving diverse viral taxa. Notably, the International Committee on Taxonomy of Viruses (ICTV) has been strongly advocating for taxon names to also reflect the evolutionary history of viruses18,19. However, the increasing use of metagenomic sequencing technologies has resulted in a large influx of newly discovered viruses that have not yet been incorporated into the ICTV taxonomy. Furthermore, it remains challenging to formally assess genetic relatedness through multiple sequence alignments of thousands of sequences comprising diverse viral taxa, particularly for those that experience a high frequency of recombination or reassortment.
In this study, we leverage the ~12 million viral sequences and associated host metadata hosted on NCBI to assess the current state of global viral genomic surveillance. We additionally analyse ~59,000 viral sequences isolated from various vertebrate hosts using a bespoke approach that is agnostic to viral taxonomy to understand the evolutionary processes surrounding host jumps. We ascertain overall trends in the directionality of viral host jumps between human and non-human vertebrates and quantify the amount of detectable adaptation associated with putative host jumps. Finally, we examine, for a subset of viruses, signatures of adaptive evolution detected in specific categories of viral proteins associated with facilitating or sustaining host jumps. Together, we provide a comprehensive assessment of potential genomic correlates underpinning host jumps in viruses across humans and other non-human vertebrates.
Source: https://www.nature.com/articles/s41559-024-02353-4
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