Why can bats can carry a large number of viruses?

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Why can bats can carry a large number of viruses?

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Why can bats can carry a large number of viruses?

Cell Heavy: The reason why bats can carry a large number of viruses: Bats has evolved a mechanism that can tolerate a large number of viral sequences.

Bats have gained notoriety in recent years for being hosts of deadly viruses. In addition to carrying an ancestral version of MERS that has had repeated outbreaks in humans, bats are also very close to the virus that caused the 2003 outbreak of severe acute respiratory syndrome, as well as the virus that caused the novel coronavirus pandemic.

They are the suspected host of the Ebola virus and the natural host of the Hendra, Nipah and Marburg viruses — all of which are potentially deadly to humans.

Why can bats live with so many viruses? Many researchers suspect that the coronavirus SARS-CoV-2 was transmitted from bats to humans either directly or through an intermediate host.

Recently, in order to produce a large number of bat tissues to study why bats are so friendly to viruses, a research team has transformed adult bat cells into pluripotent stem cells, which can be induced to form a variety of tissues and accommodate a large number of endogenous viral sequences.

These results showed that bats have evolved mechanisms to tolerate a large number of viral sequences. The study, titled “Bat pluripotent stem cells reveal unusual entanglement between host and viruses,” was published in the journal Cell .

The ability to fly, the use of throat echolocation and the ability to tolerate viruses make bats unique among mammals.

However, there are currently no reliable cellular models to study bat biology or their response to viral infection.

The researchers created induced pluripotent stem cells (iPSCs) from two species of bats: the wild giant horseshoe bat (Rhinolophus ferrumequinum) and the rat-eared bat (Myotis myotis).

iPSCs from both bat species displayed similar characteristics and had gene expression profiles similar to virus-challenged cells.

They also have a large number of endogenous viral sequences, especially retroviruses.

These results suggest that bats have evolved mechanisms to tolerate large numbers of viral sequences and that the relationship to viruses may be more complex than previously thought.

The researchers worked out the best strategy to induce bat pluripotent stem cells by continuously improving the reprogramming method.

Colonies of induced pluripotent stem cells (iPSC) from bats appeared compact and uniform, filled with tiny vesicles not found in other mammalian pluripotent stem cells.

In addition, these cells express the pluripotency factor Oct4 and proliferate at rates similar to human pluripotent cells.

Effects of reprogramming approaches on chromatin and epigenetic structure in bats

Results from the researchers’ subsequent survey of the global epigenetic landscape using transposase-associated chromatin sequencing analysis (ATAC-seq) revealed that chromatin configuration changes dramatically when bat fibroblasts transition to a pluripotent state.

Interestingly, although there is an overlap of bivalent genes in humans and bats, there are also individual specific genes for either bats or humans. Collectively, the findings suggest that bat pluripotent stem cells are both transcriptionally and epigenetically reprogrammed.

Because pluripotent stem cells often form specific tumors (teratomas) at the injection site, the researchers next injected R. ferrumequinum BiPS cells into immunocompromised mice.

Bat pluripotent stem cells eventually formed similar tumors after four to five months, consisting of immature tissue with epithelial, neural, and mesenchymal features.

These differentiation studies illustrate the potential of pluripotent bat stem cells to study important developmental events and serve as a powerful model for studying bat-specific physiological adaptations, including their reduced cancer phenotypes.

Finally, to explore whether this approach is broadly applicable to bats, the researchers created primary myotis fibroblasts from 3 mm tail biopsies of wild adult bats.

These cells exhibited co-expression of naive and primed pluripotency markers and differentiated into the three germ layers in most cells , suggesting that this approach applies to the deepest basal differences in bats.

Transcriptomic differences

The researchers collected transcriptome profiles of pluripotent stem cells from mammalian species of different developmental systems to compare them with data from the great horseshoe bat (Rhinolophus ferrumequinum), and then identified the most contributing genes to bat-specific gene expression profiles. genetic traits.

The researchers found that bat stem cells execute programs that are activated in other mammalian cells only after viral infection.

Some unique bat features may be the result of the presence of viral sequences triggering the expression of antiviral cellular programs, and most coding front genes are not under positive stress.

Endogenous viruses in bat stem cells

Throughout evolution, bats have incorporated multiple viral sequences into their genomes.

The researchers hypothesized that bat pluripotent stem cells would display a particularly rich set of expressed endogenous viral sequences and antigens compared with other mammals.

The authors first studied the abundance and diversity of endogenous retroviruses in the bat genome and found that the chromatin near the expressed endogenous retroviruses is epigenetically opened during reprogramming, that is, the reprogramming process is the result of The cause of multiple endogenous retroviral (ERV) sequences revealed in bat stem cells .

Bat cells are capable of producing ERV antigens and, in some cases, may produce active endogenous virus-like assemblies on an unusual scale compared with other mammals.

Summary

Bats have evolved an unusual way of life among mammals when they fly, use echolocation and have a curious affinity for viruses.

One possibility is that bats have evolved tolerance to viruses by evolving changes in their innate immunity, similar to the viral evasion mechanisms of mammalian immune responses.

Another possibility is that bats have evolved cellular programming mechanisms that support viral replication and persistence, similar to the way viruses manipulate host cells.

The presence of potentially important endogenous and exogenous viral products in bat pluripotent stem cells without severely impairing their ability to proliferate and grow exceeds the response of other pluripotent stem cells to viruses.

Vincent Munster, a virologist at the National Institute of Allergy and Infectious Diseases in the United States, said: “We have discussed how to use these pluripotent stem cells, which is a remarkable study. If the work in this paper can be replicated in other populations of different bat species, the impact would be huge.

source:

https://www.science.org/content/article/how-do-bats-live-so-many-viruses-new-bat-stem-cells-hint-answer

https://www.cell.com/cell/fulltext/S0092-8674(23)00041-7

Why can bats can carry a large number of viruses?

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