Research led by the University of Oxford's Big Data Institute has discovered a novel, highly virulent strain of HIV in the Netherlands. The new HIV variant results in a higher viral load and faster disease progression. The evolution of the variant, which originally emerged over two decades ago, demonstrates how viruses don’t necessarily evolve to become less severe.
The new discovery arose out of an ongoing project dubbed BEEHIVE (Bridging the Epidemiology and Evolution of HIV in Europe). Begun in 2014, the project is working to understand how genetic mutations in the HIV virus influence differences in disease.
The researchers first identified the novel HIV variant in 17 patients, and the constellation of mutations detected in it were suspected to correlate with increased viral load in patients. Further work analyzing over 6,700 HIV cases in the Netherlands revealed another 92 individuals with this particular variant.
Dubbed the VB variant, the research found those with this particular type of HIV had between 3.5 and 5.5 times higher viral loads compared to those with the more common B subtype of HIV. Another feature of the VB variant is a faster decline in CD4 immune cells, meaning the virus more swiftly damages the immune system, leading to faster development of AIDS.
“Without treatment, advanced HIV is expected to be reached in only nine months from the time of diagnosis for VB individuals, compared with 36 months for non-VB individuals, in males diagnosed at the age of 30 to 39 years,” the researchers write in the new study. “Advanced HIV is reached even more quickly in older age groups, and there is considerable variation between individuals around these expected values.”
Tracking the genomic patterns in the identified VB cases the researchers estimate the variant most likely emerged in the 1990s. In the Netherlands it is suspected cases of VB increased peaked around 2008 and have been declining in prevalence since then.
Lead author on the study Chris Wymant says the public should not be concerned about the discovery of this HIV variant. VB has been circulating for many years now and hasn’t broadly affected the dynamics of HIV spread. Instead, Wymant points out the findings demonstrate how viruses don’t intrinsically evolve to become less virulent.
“Some people say that SARS-CoV-2 will evolve to become milder, as though this can be taken for granted; it cannot,” said Wymant. “Much theoretical work has considered the balancing factors that determine the direction of evolution of virulence for pathogens, but we have very few real-world examples from which to draw general conclusions.”
In a perspective piece published alongside the new study, evolutionary biologist Joel Wertheim called the findings an example of how viruses don’t necessarily evolve to become less virulent over time. He says the relationship between virulence and transmission can influence viral evolution but this relationship is different depending on the given virus.
“The evolution of virulence – the degree to which a pathogen sickens, kills, or otherwise reduces its host’s fitness – depends on the biology of infection and transmission,” explained Wertheim. “A more virulent virus may be less transmissible because in killing its host, it reduces the opportunity for transmission. But virulence and transmissibility can be intrinsically linked, so that to maintain or increase infectiousness, a virus must be virulent.”
So in terms of HIV, for example, virulence and transmission are inextricably linked. When one is first infected with HIV the initial viral load stabilizes at a point that leads to a chronic infection that can last for years.
This initial load is referred to as the set-point viral load. The higher that set-point viral load, the faster the condition will progress to AIDS and the more infectious a person will be during that time. This means the HIV virus is unlikely to evolve to become less virulent.
Looking at SARS-CoV-2, Wertheim says it certainly is possible the virus could evolve to cause less severe disease but, “this outcome is far from preordained.” The direction this novel coronavirus takes depends on how it balances transmission and virulence.
So far, Wertheim points out, it is clear SARS-CoV-2 is becoming more transmissible but we have also seen variants that are significantly more virulent. This indicates there is no reason right now that natural selection would privilege a less virulent form of the virus.
“SARS-CoV-2 variants demonstrate that this virus is repeatedly evolving to be more transmissible, and not all of these adaptive variants are demonstrably more virulent,” Wertheim said. “However, the Delta variant that dominated global cases in late 2021 shows how SARS-CoV-2 could evolve to be both more transmissible and more virulent. The Omicron variant is more transmissible, but whether it is more or less virulent in immunologically naïve individuals is unclear.”
Wymant says his HIV research is a pertinent reminder that “prevention is better than cure.” He says what seemed to slow the spread of the VB variant in the late 2000s were strong infection control and treatment measures in the Netherlands. Essentially, the best way to reduce the impact of new virus variants on a community is to reduce transmission.
“It is said, correctly, that it is not in any virus' interest to kill the people it infects so quickly that they cannot pass it on to others,” said Wymant. “However, there is a lot of room for the virus to maneuver before reaching that extreme stage. As it explores the space of possible mutations, if it finds a combination that increases transmissibility and causes more damage at the same time, such a variant is expected to outcompete others and spread widely.”
The new study was published in the journal Science.
Source: University of Oxford
