On the go: A virus that has been rampant among monkeys so far could also be dangerous for humans – and then cause an Ebola-like fever. Because the Simian Hemorrhagic Fever Virus (SHFV) can penetrate and multiply in human cells, as a study reveals. In human cell cultures, the pathogen reached high viral loads and appeared to be largely immune to the cell’s own defense mechanisms. The researchers do not rule out that there are even undetected cases among humans in Africa.
Not only are monkeys our closest relatives, they also share many immunological traits with us humans. As a result, there are many diseases and pathogens that can spread from monkeys to humans and vice versa. So can yourself apes infected with the SARS-CoV-2 coronavirus AIDS pathogen HIV again jumped from apes to humans at the beginning of the 20th century. monkey pox again, while having their reservoir host in rodents, they can affect both monkeys and humans.
Causative agent of hemorrhagic fevers in monkeys
Cody Warren from the University of Colorado in Boulder and his colleagues have now identified a new candidate for the species leap from apes to humans. It is the Simian Hemorrhagic Fever Virus (SHFV), a pathogen belonging to the RNA viruses that mainly affects rhesus monkeys, pasque monkeys and other monkeys. The virus, also known as delta arterivirus, can cause a severe hemorrhagic fever and lead to death, similar to Ebola.
The worrying thing about it: Outbreaks have also been reported in primate stations and in 2021 scientists found that the SHF virus can also affect chimpanzees and gorillas – the closest relatives of humans. In addition, like most RNA viruses, the pathogen has a relatively high mutation rate and can also cause long-lasting, asymptomatic infections in some monkey species. “It is therefore important to find out whether these monkey viruses also have the potential to infect humans,” emphasize Warren and his team.
Infection via intracellular docking site
For their study, the researchers first determined which docking sites the SHF virus uses for its infection. Comparisons of susceptible and non-susceptible cells and experiments with genetically modified monkey cells revealed that the monkey virus, like Ebola, Lassa and other causative agents of hemorrhagic fever, uses an intracellular receptor for infection. To do this, the virus can first be surrounded by the cell membrane so that it is constricted inwards in a membrane vesicle.
“After these viruses have penetrated the cell, they dock to receptors on the membrane of the endosomes,” the scientists explain. Only this docking enables the virus to leave the membrane vesicles and reach the cytoplasm. The cell tests showed that the SHFV uses the CD163 receptor as an intracellular docking site – a receptor that occurs in monkeys, great apes and also humans.
Compatible also with human receptor
Further experiments showed that the simian virus can also use the CD163 docking sites of great apes and humans: “We found that the Simian Hemorrhagic Fever Virus is fully compatible with all great ape CD163 variants tested,” report Waren and his team. “This includes the human variant of CD163, which allowed robust replication of SHFV.” Typically, these docking sites are found primarily in macrophages, the scavenger cells of the immune system.
“These findings are significant because they confirm that SHFV has already cleared the first hurdle of a successful species jump to humans: the SHFV virions can invade cells that have the human CD163 variant,” the researchers state. Next, they used two human cell lines to investigate whether the monkey virus can also multiply in the human cell environment and resist the cell’s own defense mechanisms.
Proliferation in human cells
The result: The SHF virus can multiply in human cells – sometimes even to a large extent: “The wild-type SHFV showed the same replication dynamics and virus titers in the cells from the human kidney epithelium as they occur in the most susceptible monkey cell lines”, report Warren and his colleagues. The viral load in human cell culture was more than ten million infectious virions per milliliter.
This demonstrates that the simian virus SHFV is already adapted to human cells in terms of its replication. “The virus has figured out how to enter human cells and multiply there,” says senior author Sara Sawyer of the University of Colorado. “In addition, it can evade important cellular immune mechanisms that should actually protect us from such an animal virus – this is quite rare.”
“Caring for Global Health”
According to the research team, these viruses could pose a real threat: “Our findings raise concerns for global health and pandemic prevention,” they write. “It is possible that people in Africa have already been infected with such viruses without being recognized.” This applies all the more since the Simian Hemorrhagic Fever Virus is just one of several closely related viruses in monkeys.
“Given that at least three of these simian arteriviruses have caused fatal infections after jumping in macaques, and that humans are completely immunologically naïve to these viruses, we urgently need to develop serological tests for surveillance.” However, Warren and his colleagues emphasize also that it is not yet clear how severe an SHFV infection would be in humans. (Cell, 2022; doi: 10.1016/j.cell.2022.09.022)
Quelle: University of Colorado at Boulder