Noroviruses change the bacterial microbiome – intestinal bacteria also react to an infection with enteric viruses –

Lasting consequences: We usually only feel the effects of a norovirus infection for a few days, but these viruses can also cause long-term changes in our body. For example, they bind to bacteria in our intestinal flora and trigger drastic changes: the activity of a quarter of the bacterial genes is changed and the stress reaction that is triggered even gives the bacteria a wrinkled appearance, as a research team has discovered.

When viruses infect us, they use our cells to multiply. However, noroviruses not only infect human cells, but also interact with the billions of bacteria that belong to the microbiome of our intestines. In order to gain access to their host cells, the viruses must first cross the gut microbiome, sometimes also attaching to the bacterial cells, although these are not their primary hosts.

Previous studies suggest that this interaction can affect the severity of a viral infection and also the composition of the gut flora. But what this interaction does with the bacterial species was previously unknown.

Two types of norovirus were tested

A research team led by microbiologist Chanel Mosby from the University of Florida in Gainesville has now looked at the effects of a norovirus infection on the gene expression of intestinal bacteria. To do this, they first infected the intestinal bacterium Enterobacter cloacae with the human norovirus in vitro – in a controlled environment in the laboratory. This gut bacterium was previously known to be bound by norovirus and enhance norovirus infection in the human host.

In addition, the researchers examined the effects of norovirus infection on the intestinal flora of a living organism. To do this, they infected mice with the murine norovirus, a related species that only affects mice.

Altered gene expression of gut bacteria

The experiments showed that the gene expression of the intestinal bacteria changed significantly in both scenarios. Overall, the researchers found increased or decreased activity in around a quarter of the genes. Around half of these genes responded to both types of norovirus. As Mosby and her colleagues explain, such changes in bacterial gene activity usually represent reactions of the microbes to environmental stimuli – in this case apparently the docking of the viruses.

Genes significantly affected by both norovirus species included genes associated with membrane stability and vesicle formation. As a result of this altered gene expression, the surface structures of E. cloacae were greatly altered. “The interaction with noroviruses resulted in an increased number of surface outgrowths and a disheveled appearance of the gut bacteria,” Mosby and her colleagues explain.

Gut bacteria E. cloacae increase vesicle production after norovirus binding. Yellow arrows indicate vesicles. Green/blue arrows indicate virions. © Mosby et al. / Journal of extracellular vesicles, CC-by-sa 4.0

Increased vesicle production as a stress response

The researchers then went one step further: “Based on the observation of the changed surface of the intestinal bacteria and the changed gene expression, we measured the vesicle production with and without the influence of the norovirus,” they explain. They found out: This vesicle production of E. cloacae and two other commensal bacterial species was significantly increased after an interaction with both human and murine norovirus.

The research team classifies the increased vesicle production as a stress response of the intestinal bacteria to the binding of the norovirus and also sees this as the trigger for the changed bacterial surface: The vesicles are formed by pinching off the outer membrane, which are then released from the bacterial cell as small vesicles. An increased production of these vesicles could have led to the changed appearance of the bacteria.

The researchers’ assumption was confirmed when they took a closer look at the contents of the vesicles: they contained a significantly increased number of proteins associated with bacterial stress response to changing environmental conditions.

Intestinal bacteria could increase norovirus infection

The binding of the norovirus to intestinal bacteria thus results in increased vesicle production and changes the protein content and even the size of the vesicles, which the researchers found to be significantly reduced. “We speculate that these vesicles function as a mechanism for bacterial amplification of norovirus infection by facilitating virus entry into host cells,” Mosby and her colleagues explain.

The exact role of the vesicles as supporters of viral replication in human cells is to be investigated in further studies. (Journal of extracellular vesicles, 2022; doi: 10.1002 / jev2.12172)

Quelle: University of Florida

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