Dengue: A virus by any other name. Why scientists are renaming viruses

In the final decades of the 16th Century, doctors began reporting outbreaks of a new infectious disease appearing around the world. In Philadelphia, Puerto Rico, Java and Cairo, people were experiencing an illness characterised by a fever and crippling pains across the whole body, which they called "break-bone fever" (or "quebranta huesos" in Latin America).

Around 30 years later, in 1801, an outbreak in Madrid saw the Queen of Spain at the time – María Luisa de Parma – afflicted by the disease. In a letter she wrote as she recovered, the Queen described some of her symptoms and referred to the disease by a name that will be more familiar to us today – dengue.

"I'm feeling better, because it has been the cold in fashion, that they call dengue," she wrote. "Since yesterday I've had some blood, which is what is making me uncomfortable, and after talking some time the throat hurts."

We now know that dengue fever is caused by four closely related viruses in a group known as the flaviviruses. They are spread by particular species of mosquitoes, Aedes aegypti and Aedes albopictus in tropical and subtropical regions of the world. Outbreaks can occur wherever these insects are naturally found and can affect large numbers of people. In the first four months of 2024, more than 7.6 million cases of dengue, and 3,000 deaths, were reported to the World Health Organization (WHO), surpassing the 6.5 million cases reported in the whole of 2023.  By the start of July 2024, the WHO's global dengue surveillance system had recorded 9.6 million cases – the highest incidence on record – and 5,366 deaths globally. There were 7,300 deaths from dengue reported to the WHO in 2023.

The incidence of the disease has risen rapidly over the past five years, with climate change and the El Niño climate pattern bringing warmer, wetter conditions that have allowed the insects that carry the virus to spread to new areas and amplified the disease's transmission.

The virus has been found to be actively transmitting in 90 countries in 2024, with 31 countries reporting higher-than-usual case numbers. The greatest increase in cases being seen in the Americas and in June 2024, the Centers for Disease Control and Prevention (CDC) issued a health alert about the increased risk of dengue virus infections in the US.

But the story of how dengue got its name offers an insight into the intriguing and often rather random world of virus naming. Many viruses earn their name through their symptoms, while others have been named after the location and even the animal they were first discovered in. Others have their etymology lost in the mists of time. As powerful analytic techniques make it easier to identify viruses, the list of known viruses is growing rapidly. In response, scientists are trying to establish some order from the chaos, developing systematic naming systems that make it easier to identify and classify new viruses as they emerge.

The exact origin of the name dengue is a little uncertain, but it is related to the symptoms

There are currently 14,690 known species of virus to have been officially classified, but scientists how no clear picture of just how many different viruses exist out in the world. For example, mammals alone are estimated to harbour 320,000 viruses, while another recent study of the human gut uncovered 140,000 bacteriophages – a type of virus that infects bacterial cells.

Around 270 viruses are known to infect humans, but that list too is growing all the time, with the emergence of new infectious diseases caused by viruses such as Sars-CoV-2, the Zika virus and Mpox.

The exact origin of the name dengue is a little uncertain, but it is related to the symptoms. People with the infection feel as though their bones and muscles are seizing up, which makes movement painful and awkward. One theory is that dengue might be derived from the Spanish version of an Swahili term for the disease, ki denga pepo, which meant a sudden overtaking by an evil spirit. Alternatively, it could have come from the way people pronounced "dandy" in the Caribbean, where the disease is most commonly found, or the Spanish equivalent "dengeruo", in reference to the stiff, uncoordinated gait of those afflicted by the disease.  

The latter would seem to be a somewhat jovial way of describing a rather nasty disease.

Dengue virus belongs to a group of viruses called haemorrhagic fever viruses. Many are spread via mosquito bites, some are transmitted by ticks, and a few can spread to people from other mammals such as bats, and others even person to person, through direct contact with blood and body fluids. They all cause symptoms which include high temperature, severe headache, pain in joints and muscles, diarrhoea and vomiting, as well as bleeding and bruising in random places around the body. Not everyone will produce noticeable symptoms, but viral haemorrhagic fevers can be very nasty. They include Ebola, Nipah and Marburg viruses, which have high fatality rates and are exceptionally unpleasant diseases.

How the viral haemorrhagic fevers (VHFs) earned their names, however, is fascinating. Some come from a portrayal of the symptoms, as with dengue.

There is another mosquito-borne viral haemorrhagic fever which affects the liver and causes jaundice in patients. It is not entirely surprising that people decided to call it Yellow Fever. This brings us, however, to one problem of using symptoms as the basis of a virus name – often other infections have similar symptoms.

Many liver infections can lead to jaundice, where the white of the eyes, urine and occasionally skin, yellow. The Hepatitis A, B, C, D and E viruses are good examples, but the Epstein-Barr virus, which causes glandular fever and is named after two of the scientists who discovered it – pathologist Michael Epstein and virologist Yvonne Barr – also causes liver damage that can lead to jaundice. The Rubella virus, which causes German measles and is another symptom-based name that derives from the Latin for "little red" after the rash it causes in sufferers, has also been found to cause liver issues in rare cases, particularly in newborns.

Some viruses have even found themselves named after two different places, thousands of miles apart

Even some of the more interestingly named viruses can trace their names back to descriptions of the symptoms they cause. Chikungunya – a debilitating mosquito-borne virus that causes fever and severe joint pains – can be translated to "that which bends up" from Kimakonde, the local language from the part of Tanzania in East Africa where the disease was first recognised. Its name refers to the agonised posture that many patients infected with the virus adopt. Another related virus that causes almost indistinguishable symptoms to Chikungunya is O'nyong'nyong, which translates from the Acholi dialect in Northern Uganda as "very painful weakening of joints".

Then there are the viruses that denote the place where the virus was first identified. The virus associated with Bolivian Haemorrhagic Fever, for example, is called Machupo Virus, after a river in San Joaquin, Bolivia, close to where the first outbreak was identified in 1959.

But some viruses have even found themselves named after two different places, thousands of miles apart. In early 1967, a team of scientists and doctors, working in what is now the Democratic Republic of Congo, reported details of a virus responsible for outbreaks of a mysterious viral haemorrhagic fever in the region since the 1950s. Later in 1967, a Russian virologist published the identifying features of a virus causing a tick-borne haemorrhagic fever symptoms that had been circulating in the Crimea peninsula among Soviet military personnel since the 1940s.

On closer examination, the two viruses were considered to be identical, leading to the combined name of Crimean-Congo Haemorrhagic Fever (CCHF). A large outbreak of infections by this virus in Iraq during the first half of 2022 caused 212 cases of Crimean-Congo Haemorrhagic Fever and claimed 27 lives. There are also fears the disease could appear in new areas as the changing climate allows the ticks that carry the virus to spread further north into parts of Europe such as France, Italy, Spain and the Balkans.

The names given to viruses when they first discover them can be misleading too. Mpox is an animal disease which pass to humans – something known as a zoonosis. It was known as Monkeypox until 2022, when the WHO recommended renaming it Mpox in an attempt to stem the racism and stigmatisation that had accompanied the old name.

The reason for the virus being named Monkeypox in the first place was because it was first noted in monkeys imported to Europe from Central Africa for research. However, the monkeys were accidental hosts – the main natural hosts are rodents, including the African rope squirrel.

The virus is in the same classification family as smallpox (Orthopoxvirus), but not all viruses with "pox" in the name are related. The chickenpox virus, which is more formally called Varicella-zoster virus, is actually related to the virus that causes cold sores and genital warts, the herpes simplex virus.

How viruses are diagnosed

The first half of the 20th Century saw significant advances in microscopy, which enhanced the ability to detect and identify viruses. Most viruses are too small to be found under a normal light microscope, however powerful its resolution. But the advent of the electron microscope allowed the detection and characterisation of many significant viruses. This was how the Hepatitis B virus, for example, was discovered in 1970.

Virology in the 21st Century has even more tools at its disposal, including rapid sequencing of the genetic material of viruses. Powerful whole-genome sequencing technologies also allow scientists to find all the genetic material in a sample and,  with the help of computers, match it to known viruses. It can also help identify unknown viral sequences, as happened when scientists in Wuhan identified the new coronavirus, Sars-CoV-2, in 2019

It also has nothing to do with chickens. Rather, the common name stems from the blisters it causes looking a little like chickpeas (although other theories suggest it was because children in the midst of an infection looked as though they had been pecked all over by chickens). The formal virus name "varicella" comes from the Latin for spots (the large pocks full of fluid and virus all over the body in chickenpox)  and "zoster" means belt, which refers to the defined bands of spots people with shingles experience. But over the past 40 years that formal identification has continued to be refined and its official name has changed to the slightly weird sounding Varicellovirus humanalpha3. 

And this underlines how the approach to virus naming has undergone something of a transformation in recent years.

While naming viruses after symptoms or places can have a strange kind of romantic appeal, as a system for categorising viruses, it lacks the logic and order that virologists need. Scientists need to understand biological relationships to help them devise diagnostic tests and develop anti-viral treatments. They can help predict how emerging viruses may behave and assist in vaccine development.

It has led scientists at the International Committee on Taxonomy of Viruses – a body that maintains the list of viruses with approved names – to seek out better ways of bringing order from the chaos.

Advances in genetic sequencing technology has meant that scientists are far better equipped to identify whether viruses are related to one another or not. Some that cause similar symptoms, for example, can actually be caused by dramatically different viruses. If we look again at the viral haemorrhagic fevers, they can be caused by four distinct families of viruses.

How they are grouped together depends on their genetic make-up. You might be familiar with the intertwined strands of DNA that are found within our own bodies – the famous double helix –along with all other living things, from bacteria, to plants, to animals. But things get a lot more complicated in the world of viruses. Some viruses do have this double strand of DNA , but others can only have one.

Many viruses, including those that cause nasty disease such as viral haemorrhagic fevers, Covid-19 and flu viruses, use a different genetic material called RNA. Some carry two strands of RNA, while others carry just a single strand.

These high level genetic distinctions can be quite helpful for understanding relationships between viruses and is the basis of a classification system designed by and named after Caltech virologist David Baltimore. In this system, viruses are placed into one of seven groups based upon the type of genetic material they carry. For viruses which use DNA for their genome, it is quite straightforward – Group I are double-stranded DNA viruses and Group II have single-stranded DNA. Group III are double-stranded RNA viruses.

Some viruses have a single strand of RNA which can directly hijack the cellular tools that translate genetic material into proteins in the cells they infect. These are known as positive-sense RNA viruses and form Group IV. For others, the RNA code needs extra processing in the cell before it can be translated and these are known as negative-sense RNA viruses, forming Group V.

When trying to identify a virus, virologists look for differences rather than similarities

Two additional categories were created for tricky viruses which do not fit into any of these main groups. Group VI comprises RNA viruses where the genetic material is converted into DNA as a key part of their life cycle, such as the Human Immunodeficiency Virus (HIV). Viruses in group VII use double stranded DNA but one of the strands is incomplete, so a piece of RNA has to be made along the way – an example of this is Hepatitis B virus.

But this isn't where it ends. Let's look at two viruses that produce similar symptoms in the people they infect. Dengue virus is a positive sense RNA virus, as is Chikungunya, but if we look at the details within their genetic code in more detail, it is clear that they diverge quite considerably.

When trying to identify a virus, in a sample from a patient for example, virologists look for differences rather than similarities. The group of all single-stranded positive-sense RNA viruses is helpful, but it is too broad. So, another, complementary, classification system uses principles similar to a method that was developed to classify all biological organisms – known as the Linnean method, after Swedish biologist Carl Linnaeus.

This taxonomic scheme is where the ICTV comes in. It categorises viruses into Realms, Orders and Families. Under this system, the Dengue virus is in the family Flaviviridae and the genus Flavivirus, along with Yellow Fever virus. Chikungunya, by comparison is grouped within the Togaviridae family and the Alphavirus genus alongside O'nyong'nyong.

Committees of experts at the ICTV deliberate and assess the grouping of viruses as new science emerges and change their taxonomy accordingly. The ICTV can also settle disputes about naming. A good example of this occurred in the mid 1980s, when a new virus was identified as the cause of Acquired Immune Deficiency Syndrome (Aids). There were two candidate names – Human T -Cell Lymphotropic Virus-III (HTLV-III) and Lymphadenopathy Virus (LAV) proposed by the principal research teams involved in isolating and characterising the virus. But they could not agree and no one wanted to compromise, so the ICTV decided on Human Immunodeficiency Virus (HIV), which has been used universally ever since.

But they have their work cut out. Next generation genetic-sequencing technologies are causing the number of known viruses to grow rapidly. Five years ago, there were around 800 known species of virus, says Peter Simmonds, professor of virology at the University of Oxford, UK, and a chair of an ICTV subcommittees that deliberates on the grouping of viruses. The number now listed in the ICTV's catalogue is now approaching 15,000.

Most of the known viruses are not known to cause diseases, but those that do tend to be given recognisable names in addition to the official designations allocated by the ICTV's taxonomy. The ICTV's "role is in the way they are classified, although there is some overlap in the virologists who are doing the naming and the classifying", says Simmonds. He points out that it was "an ICTV study group which came up with the name Sars-CoV-2" for the new coronavirus in 2019.

With the speed of discovery, the number of viruses that need to be grouped in the ICTV's taxonomy could soon approach 100,000, says Simmonds.

And even this could be a  conservative estimate, says Jens Kuhn, lead virologist at the National Institute of Allergy and Infectious Diseases (NIAID) Integrated Research Facility, in Fort Detrick, Maryland, and an expert on Ebola virus. ( another VHF) and is the chair of one of the ICTV subcommittees deliberating the grouping of viruses.  

When all species were re-named, a lot of virologists were very surprised – Peter Simmonds

"Viruses are gorgeous from the scientific point of view," he says. Kuhn is the chair of another ICTV subcommittee tasked with making sense of the huge numbers of viruses now being discovered. "With every new virus discovered, it gets more and more complicated."

And this recently led the ICTV to review the categorisation of all viruses to describe them in terms of genus and species, as is done in the rest of biology.

"When all species were re-named, a lot of virologists were very surprised," says Simmonds.

But these official names are important for ensuring scientists can communicate effectively as they increasingly collaborate with colleagues around the world, says Kuhn. The Covid-19 pandemic saw international scientific collaboration on an unprecedented scale as researchers shared data and worked together to tackle the global threat posed by the Sars-CoV-2 virus.

"Species names are spelt the same everywhere in the world," says Kuhn. "They are Latinised and use the Latin alphabet." This means there can be no doubt which virus is being referred to in a formal setting.

But as humans we have a need to label things and the name needs to be memorable, he admits. "We celebrate virus diversity by language diversity," he says, giving the example of Ebola. "It sounds intriguing, so it has resonance."  The official ICTV name Orthoebolavirus zairense is less likely to stir the imagination.

And as for dengue virus? In 2022 the ICTV renamed it too. It now goes by the far less catchy name of Orthoflavivirus denguei. More organised, for sure, but a mouthful that might even have given the fluid pen of the Queen of Spain cause for pause.

-bbc