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Posts Tagged ‘hibernation’

Viral peek-a-boo

Posted in Cell Biology, Cell Biology, Signaling & Cell Circuits, Clinical Genomics, Disease Biology, Proteomics, Viral diseases, Virology - Vector-borne DIsease, tagged , , , , , , on November 16, 2018| Leave a Comment »

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Once herpes simplex infects a person, the virus goes into hiding inside nerve cells, hibernating there for life, periodically waking up from its sleep to reignite infection, causing cold sores or genital lesions to recur. Research from Harvard Medical School showed that the virus uses a host protein called CTCF, or cellular CCCTC-binding factor, to display this type of behavior. Researchers revealed with experiments on mice that CTCF helps herpes simplex regulate its own sleep-wake cycle, enabling the virus to establish latent infections in the body’s sensory neurons where it remains dormant until reactivated. Preventing that latency-regulating protein from binding to the virus’s DNA, weakened the virus’s ability to come out of hiding.

 

Herpes simplex virus’s ability to go in and out of hiding is a key survival strategy that ensures its propagation from one host to the next. Such symptom-free latency allows the virus to remain out of the reach of the immune system most of the time, while its periodic reactivation ensures that it can continue to spread from one person to the next. On one hand, so-called latency-associated transcript genes, or LAT genes, turn off the transcription of viral RNA, inducing the virus to go into hibernation, or latency. On the other hand, a protein made by a gene called ICP0 promotes the activity of genes that stimulate viral replication and causes active infection.

 

Based on these earlier findings, the new study revealed that this balancing act is enabled by the CTCF protein when it binds to the viral DNA. Present during latent or dormant infections, CTCF is lost during active, symptomatic infections. The researchers created an altered version of the virus that lacked two of the CTCF binding sites. The absence of the binding sites made no difference in early-stage or acute infections. Similar results were found in infected cultured human nerve cells (trigeminal ganglia) and infected mice model. The researchers concluded that the mutant virus was found to have significantly weakened reactivation capacity.

 

Taken together, the experiments showed that deleting the CTCF binding sites weakened the virus’s ability to wake up from its dormant state thereby establishing the evidence that the CTCF protein is a key regulator of sleep-wake cycle in herpes simplex infections.

 

References:

 

https://www.ncbi.nlm.nih.gov/pubmed/29437926

 

https://hms.harvard.edu/news/viral-hideout?utm_source=Silverpop

 

https://www.ncbi.nlm.nih.gov/pubmed/30110885

 

https://www.ncbi.nlm.nih.gov/pubmed/30014861

 

https://www.ncbi.nlm.nih.gov/pubmed/18264117

 

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Fat, sleep and the gut

Posted in Cell Biology, Curation, Lipid metabolism, Metabolism, Metabolomics, Microbiology, Obesity, tagged , on February 6, 2016| Leave a Comment »

Fat, sleep and the gut

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Hibernating Bear Microbiome May Hold the Key to Combating Obesity   

GEN News Highlights  http://www.genengnews.com/gen-news-highlights/hibernating-bear-microbiome-may-hold-the-key-to-combating-obesity/81252333/

http://www.genengnews.com/Media/images/GENHighlight/107756_web1581601731.jpg

This visual abstract depicts how the microbiota and serum metabolites in brown bears differ seasonally between hibernation and active phases. Colonization of mice with a bear microbiota promoted increased adiposity. These findings suggest that seasonal microbiota variation may contribute to metabolism of the hibernating brown bear. [Sommer et al./Cell Reports 2016]

 

Gorging oneself on high-calorie food to pack on fat only to fall asleep for a few months and have it all melt away isn’t the latest diet fad (at least not yet), but it is a regular part of life for bears as they prepare to hibernate for the winter. Yet, despite the rapid weight gain, the animals somehow avoid the health consequences so often associated with obesity in humans.

Researchers at the University of Gothenburg in Sweden have published results from a study wherein they show that bears’ shifting metabolic status is associated with significant changes in their gut microbes. The researchers were particularly surprised by the discovery that the bears’ summer gut microbiota included bacteria that take in more energy from the diet.

“The restructuring of the microbiota into a more avid energy harvester during summer, which potentially contributes to the increased adiposity gain without impairing glucose metabolism, is quite striking,” explained senior study author Fredrik Bäckhed, Ph.D., professor at The Wallenberg Laboratory for Cardiovascular and Metabolic Research within the University of Gothenburg.

The findings from this study were published recently in Cell Reports through an article entitled “The Gut Microbiota Modulates Energy Metabolism in the Hibernating Brown Bear Ursus arctos.”

Previous work done in Dr. Bäckhed’s laboratory showed that the composition of gut microbiota can influence the amount of energy harvested from the diet, and more recently the investigators found that the microbiota also shifts in people who are obese and in those with type 2 diabetes. This led the team to hypothesize whether changes to the microbiota might also be important in hibernating brown bears in the wild.

“We analyzed the microbiota of free-ranging brown bears during their active phase and hibernation. Compared to the active phase, hibernation microbiota had reduced diversity, reduced levels ofFirmicutes and Actinobacteria, and increased levels of Bacteroidetes,” the authors wrote. “Several metabolites involved in lipid metabolism, including triglycerides, cholesterol, and bile acids were also affected by hibernation.”

Dr. Bäckhed’s team took their investigation a step further by exploring whether the changes in the bears’ microbiota was driving the shift in metabolism by transferring the bears’ summer and winter microbiota into mice.

“Transplantation of the bear microbiota from summer and winter to germ-free mice transferred some of the seasonal metabolic features and demonstrated that the summer microbiota promoted adiposity without impairing glucose tolerance, suggesting that seasonal variation in the microbiota may contribute to host energy metabolism in the hibernating brown bear,” described the authors.

The researchers were encouraged by their findings and believe it’s possible that the findings in bears might suggest new strategies for managing obesity in humans; however, Dr. Bäckhed urged caution about over-interpreting the study results.

“I think it’s too early [to say], as I consider this being very basic science,” Dr. Bäckhed concluded. “However, if we learn more about which bacteria and the functions that promote and/or protect against obesity [in hibernating bears], we may identify new potential therapeutic targets.”

 

The Gut Microbiota Modulates Energy Metabolism in the Hibernating Brown Bear Ursus arctos

Felix Sommer, Marcus Stahlman, Olga Ilkayeva, …, Christopher B. Newgard, Ole Frobert, Frederik Backhed

Cell Reports Feb 2016;14: 1–7.

http://dx.doi.org/10.1016/j.celrep.2016.01.026

Highlights

Bear microbiota composition differs seasonally between hibernation and active phase

Blood metabolites differ seasonally in the brown bear

The bear gut microbiota promote energy storage during summer

 

Hibernation is an adaptation that helps many animals to conserve energy during food shortage in winter. Brown bears double their fat depots during summer and use these stored lipids during hibernation. Although bears seasonally become obese, they remain metabolically healthy. We analyzed the microbiota of free-ranging brown bears during their active phase and hibernation. Compared to the active phase, hibernation microbiota had reduced diversity, reduced levels of Firmicutes and Actinobacteria, and increased levels of Bacteroidetes. Several metabolites involved in lipid metabolism, including triglycerides, cholesterol, and bile acids, were also affected by hibernation. Transplantation of the bear microbiota from summer and winter to germ-free mice transferred some of the seasonal metabolic features and demonstrated that the summer microbiota promoted adiposity without impairing glucose tolerance, suggesting that seasonal variation in the microbiota may contribute to host energy metabolism in the hibernating brown bear.

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