To shine light on the future of the relationship between humans and viruses, a team of researchers from the University of Oxford looked into the dim and distant past.
Without the capability to reproduce on their own, viruses infect other organisms, literally inserting their DNA into a host cell and taking over its processes to replicate. Various strains of viruses can infect everything from bacteria and algae to plants and humans. Much smaller than bacteria, viruses take a variety of shapes and forms, and even though they carry genetic material and evolve, the question of whether viruses are "alive" remains a contemporary scientific question.
Pressed by the infectious capability of viruses, researchers push to understand how viruses function and how we might deter the often deadly outcome of human viral infections. To better address viral challenges of the present, scientists look to history to fill in some of the blanks.
In a study published in Nature Communications, a team from Oxford University's Department of Zoology took a walk back in time to look at a family of viruses that existed long before humans, more than 500 million years ago, when vertebrates first left the oceans for the shore and the first ferns colonized fertile soil.
Unlike paleontologists who study fossil remains, like the trilobites who emerged at the outset of the Palaeozoic Era, viruses do fossil record that scientists can study. Or do they?
One special type of virus, called the retrovirus, inserts itself into its host's genetic material. DNA is located in almost all living cells and stores and transmits this hereditary information. RNA is another genetic material, which carries information between the DNA and the protein-building ribosomes in a living cell. Ribosomes are a cell structure made up of proteins and RNA that build protein out of amino acids, among other functions.
Viruses, which carry DNA or RNA strands, cannot replicate until they have a chance to invade a living cell. A retrovirus has a single-strand of RNA as its genetic material, and when the virus attaches to a cell, it inserts the RNA into it. The RNA genome is copied into DNA, a process called reverse transcription, and that DNA is put into the host's genome, where it's copied and turned into proteins. The human immunodeficiency virus (HIV) that causes AIDS is currently the best known human retrovirus. Retroviruses and their genetic material have also implicated in cancers and immunodeficiency conditions in animals.
The reason it is called "retro" is because the RNA virus uses an enzyme called reverse transcriptase to write back into the DNA of its host. This is a backward, or retro, process because genetic information usually flows from DNA to RNA, not the other way around.
Viruses cannot leave behind physical fossil remains, but retrovirus material that has integrated into the genome of a living organism is sometimes loosely referred to as a viral fossil. How does that happen? When the RNA of a retrovirus translates itself back into the DNA—there it remains, moving forward as an endogenous retrovirus (ERV). If that infected cell is a sex cell, a sperm, or egg cell in a human, that DNA can be passed down for generations to come. Not generally considered to be disease-causing in humans (some actually have important functions), ERVs might be considered genomic fossils that tell the story of viral battles of an earlier age.
In the Oxford University study, scientists sought to better understand when retroviruses emerged and started to infect organisms, and thereby better understand their relationship with vertebrate hosts like humans. Because retroviruses are commonly found across living organisms, estimates placed their age at approximately 100 million years old.
For their study, researcher Dr. Aris Katzourakis and student Pakorn Aiewsakun used a retrovirus family called foamy viruses, so-named because their structure looks like foam under a microscope. Using genetic sequencing and an analytical tool called BLAST, the study looked at the retroviral components of fish and amphibian genomes, called FL-ERVs, in 28 different marine vertebrate species including fish, frogs, salamanders, and one type of shark.
BLAST is the acronym for a bioanalytic tool called Basic Local Alignment Search Tool, which is used to line up genetic material to a database of known sequences from all walks of life and calculate how much they've changed as the species evolved apart.
Analyzing the genetic data and crunching the numbers, scientists were able to propose an emergence date—the timeline for when these viruses first infected their hosts—that was much older than suspected, noting in the paper:
Our results strongly suggest that this group of viruses originated together with their jawed vertebrate hosts in the Ordovician ocean, and underwent a water-to-land evolutionary transition with their hosts, co-evolving with one another for [more than 450 million years].
The Ordovician Period occurred within the Paleozoic Era, from about 542 million years ago to 251 million years ago. Life in the sea was abundant during Paleozoic times, but was sparse on land.
The Ordovician Period lasted about 45 million years and marked the beginning and the end of trilobites, whose fossils are commonly found in limestone shale today. Algae, early fish, cephalopods, brachiopods, and corals navigated warm currents, while primitive plants began to grow on land. In the later Ordovician Period, mass die-offs are thought to have occurred when the climate changed.
Importantly, this research places an approximate date on the adaptive duel between virus and vertebrate. "These findings show that this medically important group of viruses is at least up to half a billion years in age—far older than previously thought," Katzourakis said. "They date back to the origins of vertebrates, and this gives us the context in which we should consider their present-day activity and interactions with their hosts." He adds:
Our inferred date of the origins of retroviruses coincides with the origins of adaptive immunity, and thus it is likely that retroviruses have played an important role in the emergence of this key tool in vertebrate antiviral defense.
As new technology allows us to tease out knowledge of how viruses impact our genetic record, we have a better chance of developing methods and tools to understand how we can work with our immune system to battle viruses like AIDS in the present.