Unveiling the aquatic origins of influenza viruses: The surprising link to fish

Influenza is a serious public health risk, causing severe symptoms, hospitalisation, and death particularly in vulnerable populations such as children, elderly, pregnant women, and those with medical conditions. Due to the COVID-19 pandemic, influenza cases have increased world over. In Europe, the virus is still active despite being overshadowed by the coronavirus. In India, the government is bringing attention to the rise in influenza cases, urging citizens to take necessary precautions. Doctors in India have reported a rise in long-lasting flu cases with worse-than-usual symptoms, prompting them to urge people to get the annual flu vaccine, practice hygiene, and wear masks in public. ICMR has identified the H3N2 variant of the influenza virus as the cause of the spike, which may be attributed to multiple factors, including changing weather, air pollution, and intermingling of people after two years of following Covid protocols. Other contributing factors include air travel, environmental changes, and evolution of influenza and cold viruses, which can circulate year-round.

In a recent article published in BioRxive, a team of Australian investigators led by Mary Petrone has proved that most of the influenza viruses have an aquatic origin. Researchers have conducted extensive genetic research in an effort to trace the origin of the virus family. By analyzing evidence in the fossil record and using genetic markers, their studies suggest that the family probably originated hundreds of millions of years ago in primordial aquatic animals who evolved well before the first fishes.

What are influenza viruses?

“Influenza” derives from the Italian word for “influence” and was first used to describe an epidemic linked to planetary alignments during the 17th century. It later used to refer to similar outbreaks and, in the early 18th century, used to describe a disease with fever, headache and muscle aches. Currently, it refers to a viral infection which affects the respiratory system and is known for symptoms including fever, cough, sore throat, runny or stuffy nose, body aches, headache, chills and fatigue.

Influenza viruses are a group of RNA viruses that belong to the family Orthomyxoviridae. There are four types of influenza viruses: A, B, C, and D. Influenza A and B viruses are responsible for seasonal outbreaks of influenza in humans, while influenza C viruses typically cause mild respiratory illness, and influenza D viruses primarily affect cattle and do not infect humans.

Influenza A viruses are classified by their hemagglutinin (HA) and neuraminidase (NA) combinations. Currently, humans are affected by A(H1N1) and A(H3N2) strains. A(H1N1) is also referred to as A(H1N1)pdm09, as it caused the 2009 pandemic and replaced pre-2009 seasonal A(H1N1). Only influenza A viruses have caused pandemics. Influenza B viruses are divided into lineages, not subtypes, with current B viruses belonging to either B/Yamagata or B/Victoria lineages.

Influenza viruses are highly mutable, making them hard to treat. They are spread through respiratory droplets and cause symptoms such as fever, cough, sore throat, runny or stuffy nose, body aches, and fatigue. Usually, rest, fluids, and over-the-counter medication like acetaminophen or ibuprofen can manage the flu. Unfortunately, those with weak immune systems or underlying health conditions may suffer life-threatening complications, like pneumonia or bronchitis, necessitating medical intervention.

Origin of viruses

Viruses are simple replicating entities that have successfully parasitised all known forms of life. Many viruses have a zoonotic origin or involve the transfer of genetic material between species. Examples of zoonotic viruses include influenza, rabies, West Nile virus, Ebola virus, SARS-CoV-2, and Lyme disease. Other viruses, such as HIV, do not necessarily involve a zoonotic origin but do involve the transfer of genetic material between species, typically through a process of host-jumping.

Ocean, a rich source of virus diversity

Till today, the origin of influenza viruses was believed to be aquatic birds, particularly wild ducks, which serve as the natural reservoir for the virus. But a recent genetic analysis carried by the Australian researchers has revealed that the influenza viruses had an aquatic origin million of years ago. They used a combination of total RNA sequencing and transcriptome data mining to extend the diversity and evolutionary history of the order Articulavirales, which includes the influenza viruses. Total RNA sequencing can provide an in-depth view of the complete genetic material of a virus, and can reveal novel components and determine evolutionary relationships between distinct species in a virus family. Transcriptome data mining can be used to extract and analyze the sequences of viral proteins based on those observed in mRNA expression. This can provide insight into the evolutionary linkages between viral proteins and the evolution of viral proteins. Combining these data sets can provide a detailed view of the evolution of the order Articulavirales, including the influenza viruses. This can help to identify and characterize novel viral components in this group, as well as provide insight into the evolution of influenza viruses and provide a basis for understanding their behavior.

Corals infected by viruses!

In this study, scientists identified the first instance of Articulavirales in the Cnidaria (including corals), constituting a novel and divergent family that they tentatively named the Cnidenomoviridae. The discovery of this novel family of viruses contributes to our understanding of the evolutionary history of Articulavirales, providing evidence of the presence of the phylum among Corals and other related animals. The discovery of Cnidenomoviridae also has potential implications for coral health, as certain viruses belonging to this family are known to infect and potentially harm corals.

Invertebrate-vertebrate transmission

Evidence suggests Quaranjaviridae may have evolved in crustaceans before being transmitted to terrestrial Chelicerata (i.e. ticks). The novel Quaranjavirus was discovered in the tick Hyalomma marginatum, which is found in both aquatic and terrestrial environments. Phylogenetic analysis of viral sequences indicate a possible origin in crustaceans that spread to terrestrial chelicerates. The proximity between habitats likely aided transmission. The study also uncovered a distinct strain of influenza virus in sturgeons, indicating fish may be the initial source of this virus lineage.

The Articulavirales has evolved over 600 million years, originating in aquatic animals. Analysis revealed two clades, which correspond to distinct life styles and host ranges, hinting towards novel virus families and potential evolutionary trajectories. Host jumps and aquatic-terrestrial transitions, some of which are ongoing, shaped this evolution rather than virus-host codivergence. These findings open up new possibilities for understanding virus-host interactions, virus family evolution and the Articulavirales, necessitating further research.

Need an ecosystem-based approach

Focus surveillance efforts on ecosystems with many host generalist viruses, as these are more likely to spill over into humans or other species. Utilise tools such as molecular fingerprinting, next generation sequencing, and phylogenetic analysis to identify, characterise, and track viruses. In addition, monitor animal populations and wildlife habitats to identify hotspots, animal movements and trade to observe transmission, and water and soil samples to identify presence and abundance of viruses. To better understand ecosystems, a longitudinal, ecosystem-based metagenomic surveillance is proposed. This entails regular sample collection and analysis over time to track changes in microbial diversity, abundance, and presence of specific bacterial/viral sequences.

Researchers can use this approach to analyse microbial processes associated with climate change, pollution and human impact on the environment. By studying changes in microbial community interactions, populations and biogeography resulting from climate changes or pollution, areas of concern or further research can be identified. Monitoring changes in microbial communities impacted by changing temperature and pollutants gives insight on the ecosystem’s health and can inform decision-making for restoration. Also, studying certain microbial populations’ presence and interactions can indicate their adaptation and resilience to climate and pollution.

Conclusion

The frequency of epidemics is projected to increase as a consequence of climate change and human activities. Temperature increases, changes in precipitation, and alterations in land cover due to development of urban areas and agricultural practices can all contribute to increased risk of epidemics. More frequent extreme weather events can disrupt normal disease dynamics, allowing for the emergence of epidemics. Higher temperatures and shifts in vegetation can both lead to changes in the seasonal abundance of the vectors of infectious diseases, leading to increased potential for transmission. The increase of human travel and trade can further accelerate the spread of epidemics. Additionally, environmental changes can lead to the emergence of novel pathogens and the expansion of existing ones to new areas.

Additional Reading

• Petrone ME, Holmes EC, Harvey E (2023). Through an ecological lens: An ecosystem-based approach to zoonotic risk assessment: An ecosystem-based approach to zoonotic risk assessment. EMBO Rep. 24(2):e56578. https://doi.org/10.15252/embr.202256578.

• Petrone ME et al. (2023). Evidence for an aquatic origin of influenza virus and the order Articulavirales. Preprint at bioRxiv doi: https://doi.org/10.1101/2023.02.15.528772

• Zayed AA et al. (2022). Cryptic and abundant marine viruses at the evolutionary origins of Earth’s RNA virome. Science 376: 156–162. https://doi.org/10.1126/science.abm5847.