The Other Side of Viruses

How humans and viruses evolved together and what's in our future.

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Viruses are genetic parasites mostly known for their ability to induce disease in their host. Apart from causing harm, viruses have also played a critical role in contributing to what we know today as the human species.

In the long, complicated human-virus relationship viruses shaped evolutionary changes in the human species and the ecosystems around us. More recently, human-driven environmental changes have been accelerating shifts in global ecosystems affecting the domain of viruses. These changes are leading to a higher rate of viral emergence and creating opportunities for animal-specific viruses to transition to humans posing an increasing threat to the survival of the human species.

A major driver of human evolution

The human and chimpanzee genomes have evolved and diverged from common ancestors about five million years ago. Scientists discovered to a great surprise that these two genomes were about 99% similar to each other in coding regions, meaning that just looking at the coding sequences there was almost no genetic difference between the species. The differences lie in the non-coding part of the DNA. For a long time, scientists disregarded the parts of the DNA that they called “Junk DNA” because this code carried no obvious purpose. It is now confirmed that the majority of the human genomic non-coding DNA is of viral origin. This viral footprint is believed to be responsible for the evolutionary acquisition of very complex human-specific characteristics, such as developmental, cognitive, social, associative learning, and behavioral capacity.

Different types of viruses are designed with different strategies for living. Acute viruses that rapidly replicate and trigger diseases did not likely co-evolve with their hosts. However, viruses that are stable in their behavior and highly specific to their host can contribute to the evolution of host complexity. Such persistence can be defined as the capacity of a virus to maintain a continued presence with its host and the ability to transition to subsequent generations. Persisting genetic parasites act by incorporating a long-term strategy to defend themselves from competition and displacement by others. This strategy ensures co-existence with the host for survival as an integral part of the host and becomes crucial to the creative evolutionary process of the host species. In this partnership, viruses enable their host to maintain certain unique characteristics. Persistent viruses have passed through sex or birth to subsequent generations and lost the ability to cause an active infection. It is these persistent viruses, called endogenous retroviruses, that differentiate human species from its ancestorial relative, chimpanzees, and are responsible for the unique genetic qualities of the human species. The viruses that make us human.

What makes us human

Around 8–10% of the human genome is of viral origin.

Human endogenous retroviruses (HERV) by far are the most common virus-derived sequence in our DNA. While most of the HERV sequences are shared by the entire human species population, more recent research based on the Simons Genome Diversity Project shows that the fraction of the viral content in the human DNA is even higher (up to 10%) than it was previously believed (8%) and that some sequences exist only in a subset of individuals.

The following are a few examples where HERVs may have played a significant role as a change agent in humans.

Strong immune response. Researchers discovered that ERVs were responsible for ramping up immune systems mechanisms and assisting hosts against the infection. For example, in the human genome, ERVs (i) contributed to a stronger innate immune system by switching on the AIM2 gene that forces the infected cell to self-destruct to prevent the infection from spreading further, and (ii) improved the adaptive immune system by editing Major Histocompatibility Complex (MHC), which promotes immune recognition and eradication of foreign substances. As a result, these ancient viruses have become ‘double agents’ helping our cells to tackle other pathogens against attacking us.

Loss of N‐glycolylneuraminic acid (Neu5Gc). HERVs may also have played a role in the loss in our lineage of Neu5Gc, a type of Sialic acid that acts as a cell‐surface receptor for many viral pathogens to infect cells. It is believed that the genetic loss of this function has been beneficial on a wide range of issues such as human resistance to certain pathogens, the improved innate immune response, and the development of the human brain.

Stem cell transformation. HERV plays a critical role in the embryonic stem cells and also responsible for keeping stem cells pluripotent, which means that they can become a cell with another function in the human body. It opens multiple possibilities for scientists to apply this capability for regenerative purposes and help patients recover from traumas and diseases. Those therapies could treat conditions such as diabetes, stroke, multiple sclerosis, Parkinson’s disease, brain, and spinal cord injury. There are more than 200 cells in the human body for which embryonic cells are the ultimate source.

But the human-virus relationship has not been all positive. Fossil viruses can also be contributing to health problems such as cancer, diabetes, and autoimmunity. Furthermore, some research suggests that a persistent host-specific virus can change its strategy to take the acute form followed by the adaption of this virus to a new host species. Today, there are more than 200 pathogenic viruses that can be harmful to humans. Will this number continue to grow and, if so, what are the likely contributing factors that could drive the emergence of new viruses?

Virus Emergence

A long history of the human-virus relationship continues to evolve in the present times. While not all viruses are harmful and some may be considered beneficial, more recently accelerating environmental and ecological changes plus human overpopulation and poverty may have a significantly adverse effect on the future of human species. Newly emerging infectious diseases causing viral pandemics such as HIV/AIDS, Ebola, Zika, SARS, and SARS-COV-2 are becoming a rising concern.

The transmission of viruses into new host populations, called virus emergence, has become a significant issue. Conceptually, virus emergence happens in a three‐step process: (1) introduction of a virus into a new host species, (2) adaption of the virus to the new host, and finally, to achieve full emergence, (3) dissemination of the virus among a large number of individuals to spread epidemically through the new host population.

Elevated risks

Many scientists agree that drivers of emergence events include modifications in climate, weather, and ecosystems, population growth, human behavior, urbanization, international travel and trade, poverty, social inequality, and intensification of livestock production. Climate changes have been suspected as a major driver in the emergence of novel viruses because the alternations in average temperature, humidity, vegetation, movement of animals, and extreme weather events are more likely to affect virus range and host availability.

In recent years, the frequency of newly identified viruses in human populations appears to be increasing, but it is important to mention that causes of the virus spillover events vary and do not normally reach full-blown emergence because, by definition, for an emerging virus to “jump hosts” the host types must be closely phylogenetically related (close evolutionary relationship between the species), and the new host environment must be optimal for wide-spread dissemination.

Likely causes of viral emergence entail a combination of changes in the environment and human behavior, especially changes in the ecosystem, how humans interact with animals (wild and domestic), and how a pathogen responds to the new environment.

Solutions

Today, more than 200 pathogenic viruses are known to cause disease in humans. Virus emergence poses increasing threats to human society, and the situation may likely get worse due to continued ecological and environmental changes. How do we, as a society, defend ourselves?

1. Strong immune response. One important approach is training immune systems to broadly recognize and defend against pathogenic viruses. This can be done naturally by maintaining a healthy immune system or activating an immune response with the help of vaccines. Other options can include the development of new innovative solutions that produce antigens, which stimulate the production of antibodies by the immune systems of humans.

2. Broad-spectrum antiviral agents (BSAA) or drugs. There is an irrefutable need to develop broad-spectrum antivirals to prevent future viral pandemics of unknown origin. Respiratory viral infections such as those that cause Coronavirus and Influenza, are acute viruses that activate and resolve quickly (unlike persistent pathogens). BSAA can be deployed against a wider spectrum of emerging viruses until more effective treatments and vaccines are developed to fight a specific pathogen.

3. CRISPR‐CAS genome editing techniques. Gene‐editing mechanisms are used for altering DNA and can be applied to suppress vector populations below levels required for sustained virus transmission, breaking epidemics, and preventing further virus dissemination. Additional research and development for broader use of this technology are necessary to apply it effectively for the treatment of various infections, on a large scale.

4. Finally, education should be included as a critical step in fighting emerging infectious viruses. On an individual level, we need to understand the importance of avoiding risky behaviors such as contact with animals, as well as maintaining personal hygiene, preventing virus transmission, and respecting natures’ boundaries. As a society, we shall continue to aggressively invest in programs controlling the spread of invasive species, sustaining wildlife habitat, combating climate change, and eliminating poverty. Success in these critical actions will lead a long way in preventing the introduction of dangerous viruses into human populations. This can only be accomplished through our individual contributions and public-private partnerships striving for the benefit of all life on the planet.

Our actions define our future

Since pre-historic times until present days, viruses have played a critical role in the design of our species, human adaptation to environmental changes, stabilization of population, and even helping fight against other pathogens. Today, humans are playing a principal role in contributing to environmental and ecological changes that impact the complex life system around us. Our actions that cause changes in climate and affect ranges of species can have unforeseen consequences on virus dynamics leading to risks of viral emergence and a rise of new infectious diseases that affect human (and other species) populations. Broad awareness of this problem and continued investments in education, technology, environmental programs, and public health are necessary to reduce the risks of inadvertent extinction of the human species.

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