Virus research is focused on spillover studies

HHemorrhagic fevers caused by viruses of the Filoviridae family are High mortality rate However, it remains poorly understood.¹ Scientists suspect that these viruses entered the human population through zoonotic spillover, Marburg virusIt has been identified in Egyptian fruit bats. Rusetus aegyptiacus.² Studying viruses from bats can provide a glimpse into how these viruses survive in their original hosts and first emerge in humans, but most studies still use human isolates.

Joseph PrescottAn immunologist and virologist at the Robert Koch Institute, he studies Marburg virus infections in Egyptian fruit bats and the animals’ immune responses to it. “The ultimate goal is to compare what’s happening in the natural reservoir with what’s happening in humans,” he explained. npj virusHe and his team looked at the activity of human macrophages. Marburg virus isolated from bats And we found that there were different responses between individuals.³

“These are important questions to better understand what’s going to happen.” Gaya Amarasinghe“What drives species to mate? And, more importantly, what is the adaptation and what happens in different species?” said , a virologist who studies host-pathogen interactions in RNA viruses at the University of Washington.

Prescott and his team isolated monocytes from blood donors, cultured them into macrophages, and infected them with a bat-derived Marburg virus that expressed a fluorescent reporter.[Bat-derived Marburg virus] “That’s probably what first infects humans, and we know that macrophages and dendritic cells are some of the first target cells, so we’re trying to model that egress,” he said.

The virus infected macrophages from all donors, with infection efficiency ranging from 10 to 80% of the cell population.To investigate this further, the team RNA-sequenced cells from five donors and examined changes in gene expression after Marburg virus infection or stimulation with lipopolysaccharide (LPS), a potent macrophage activator.

Macrophages from four of the five donors showed similar gene expression profiles upon LPS stimulation, upregulating proinflammatory cytokine and chemokine genes. However, while cells from three of these donors activated expression of antiviral chemokines and cytokines in response to Marburg virus, macrophages from two donors did not activate gene expression of immune-related genes. Furthermore, the viral loads in the supernatants from these two donors were the lowest.

“Comparison [to] “LPS was great, but what about other viruses?” asked Amarasinghe, saying it would be interesting to know whether these results were specific to the Marburg virus or general to the viruses that had infected these individuals.

The team then identified a distinct baseline gene expression profile of donor macrophages and demonstrated that macrophages in response to Marburg virus express nonintegrin-capturing dendritic cell-specific intercellular adhesion molecule 3 (DC-3).DC Sign) and multiple other C-type lectins. Examining secreted inflammatory cytokines and chemokines as a more functional readout of macrophage response, the researchers showed that macrophages from non-responders produced less C-X-C motif chemokine ligand 10 (CXCL10) compared to responders.

Amarasinghe noted that the differences in macrophage responses to Marburg virus and LPS are intriguing, but the age of the donors is not given, which might help explain why such differences exist. Prescott also acknowledged that observing the differences in donor responses was exciting for him and his team, but the current sample numbers are small. “The other thing,” he added, “is that we don’t know exactly which sequence of the virus infects humans, so this isolate may be a little different than the one that makes humans sick.”

But the new study better recreates not only the initial conditions of a spillover event, but also the substances circulating in the bats’ bodies, allowing researchers to study their responses in the future and compare them to those in humans. “This definitely fills an important gap,” Amarasinghe said.

References:

1. Mane Manohar and others Advances in Marburg (MARV) virus vaccine research following its recent re-emergence in Equatorial Guinea and Tanzania: a scoping review. Cureus2023;15(7):e42014.
2. Towner J S et al. Isolation of genetically diverse Marburg viruses from Egyptian fruit bats. PLoS Pathog. 2009;5(7):e1000536.
3. Yordanova I. A. et al. Human macrophages infected with Marburg virus isolated from Egyptian rosette bats show inter-individual susceptibility and antiviral responses. npj virus.2024;2:19.