TWiV 391: Whiter reefs, fresh breath

If you have always wanted to know what coral reefs and the human oral cavity have in common, listen as guests David Pride and Forest Rohwer talk about their work on the microbiomes and viromes of these two environments, and you’ll also understand why mucus is cool.

You can find TWiV #391 at microbe.tv/twiv, or watch or listen below.

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TWiV 355: Baby’s first virome

On episode #355 of the science show This Week in Virology, the TWiV team considers the effect of a Leishmaniavirus on the efficacy of drug treatment, and the human fecal virome and microbiome in twins during early infancy.

You can find TWiV #355 at www.microbe.tv/twiv.

TWiV 323: A skid loader full of viromes

On episode #323 of the science show This Week in Virology, the family TWiVidae discuss changes in the human fecal virome associated with Crohn’s disease and ulcerative colitis.

You can find TWiV #323 at www.microbe.tv/twiv.

How influenza virus infection might lead to gastrointestinal symptoms

influenza virusHuman influenza viruses replicate almost exclusively in the respiratory tract, yet infected individuals may also have gastrointestinal symptoms such as vomiting and diarrhea. In mice, intestinal injury occurs in the absence of viral replication, and is a consequence of viral depletion of the gut microbiota.

Intranasal inoculation of mice with the PR8 strain of influenza virus leads to injury of both the lung and the intestinal tract, the latter accompanied by mild diarrhea. While influenza virus clearly replicates in the lung of infected mice, no replication was observed in the intestinal tract. Therefore injury of the gut takes place in the absence of viral replication.

Replication of influenza virus in the lung of mice was associated with alteration in the populations of bacteria in the intestine. The numbers of segmented filamentous bacteria (SFB) and Lactobacillus/Lactococcus decreased, while numbers of Enterobacteriaceae increased, including E. coli. Depletion of gut bacteria by antibiotic treatment had no effect on virus-induced lung injury, but protected the intestine from damage. Transferring Enterobacteriaceae from virus-infected mice to uninfected animals lead to intestinal injury, as did inoculating mice intragastrically with E. coli.

To understand why influenza virus infection in the lung can alter the gut microbiota, the authors examined immune cells in the gut. They found that Mice lacking the cytokine IL-17A, which is produced by Th17 helper T cells, did not develop intestinal injury after influenza virus infection. However these animals did develop lung injury.

Th17 cells are a type of helper T cells (others include Th1 and Th2 helper T cells) that are important for microbial defenses at epithelial barriers. They achieve this function in part by producing cytokines, including IL-17A. Th17 cells appear to play a role in intestinal injury caused by influenza virus infection of the lung. The number of Th17 cells in the intestine of mice increased after influenza virus infection, but not in the liver or kidney. In addition, giving mice antibody to IL-17A reduced intestinal injury.

There is a relationship between the intestinal microbiome and Th17 cells. In mice treated with antibiotics, there was no increase in the number of Th17 cells in the intestine following influenza virus infection. When gut bacteria from influenza virus-infected mice were transferred into uninfected animals, IL-17A levels increased. This effect was not observed if recipient animals were treated with antibiotics.

A key question is how influenza virus infection in the lung affects the gut microbiota. The chemokine CCL25, produced by intestinal epithelial cells, attracts lymphocytes from the lung to the gut. Production of CCL25 in the intestine increased in influenza virus infected mice, and treating mice with an antibody to this cytokine reduced intestinal injury and blocked the changes in the gut microbiome.

The helper T lymphocytes that are recruited to the intestine by the CCL25 chemokine produce the chemokine receptor called CCR9. These CCR9 positive Th cells increased in number in the lung and intestine of influenza virus infected mice. When helper T cells from virus infected mice were transferred into uninfected animals, they homed to the lung; after virus infection, they were also found in the intestine.

How do CCR9 positive Th cells from the lung influence the gut microbiota? The culprit appears to be interferon gamma, produced by the lung derived Th cells. In mice lacking interferon gamma, virus infection leads to reduced intestinal injury and normal levels of IL-17A. The lung derived CCR9 positive Th cells are responsible for increased numbers of Th17 cells in the gut through the cytokine IL-15.

These results show that influenza virus infection of the lung leads to production of CCR9 positive Th cells, which migrate to the gut. These cells produce interferon gamma, which alters the gut microbiome. Numbers of Th17 cells in the gut increase, leading to intestinal injury. The altered gut microbiome also stimulates IL-15 production which in turn increases Th17 cell numbers.

It has been proposed that all mucosal surfaces are linked by a common, interconnected mucosal immune system. The results presented in this study are consistent with communication between the lung and gut mucosa. Other examples of a common mucosal immune system include the prevention of asthma in mice by the bacterium Helicobacter pylori in the stomach, and vaginal protection against herpes simplex virus type 2 infection conferred by intransal immunization.

Do these results explain the gastrointestinal symptoms that may accompany influenza in humans? The answer is not clear, because influenza PR8 infection of mice is a highly artificial model of infection. It should be possible to sample human intestinal contents and determine if alterations observed in mice in the gut microbiome, Th17 cells, and interferon gamma production are also observed during influenza infection of the lung.

TWiV 313: With viruses like these, who needs enemas?

On episode #313 of the science show This Week in Virology, Vincent, Alan, and Rich discuss how norovirus, an enteric virus, can replace the functions of the gut microbiome.

You can find TWiV #313 at www.microbe.tv/twiv.

TWiV 286: Boston TWiV party

On episode #286 of the science show This Week in Virology, Vincent and Alan meet up with Julie and Paul at the General Meeting of the American Society for Microbiology in Boston, to talk about their work on the pathogenesis of poliovirus and measles virus.

You can find TWiV #286 at www.microbe.tv/twiv.

Bacteria in our brains

bacteria in brainMicrobial communities are found at many different sites on the human body, including nasal passages, oral cavities, skin, gastrointestinal tract, and urogenital tract. These commensal microbes shape the immune and metabolic status of the host and play important roles in human health and disease. The brain is one organ that has been assumed to be sterile in the healthy host, but this is probably not true – apparently we have bacteria in our brains!

This remarkable observation came about as part of a study to determine if AIDS, a disease known to damage the blood-brain barrier, might lead to the presence of bacteria in the brain. Autopsy-derived cerebral white matter was obtained from AIDS patients; controls included material from individuals who died of other causes (including cerebral infarction, meningitis, and encephalitis), and also brain tissue collected during surgical resection for epilepsy. Total RNA was prepared, copied into DNA, and subjected to massively parallel sequencing. The results showed that all patient samples contain sequence tags for alpha-proteobacteria (>70% of bacterial sequences). Other bacteria representing 30% of the sequences were not universally present. Alpha-proteobacteria do not predominate in other body sites where the microbiomes are dominated by Firmicutes, Bacteriodetes and Actinobacteria. Staining of sections of human brain with antibodies to peptidoglycan, a component of the bacterial cell wall, suggest that the bacteria are localized mainly in glia (photograph).

To demonstrate that live alpha-proteobacteria are present in the brain specimens, homogenates of brain samples were prepared and inoculated intracerebrally into immunocompromised mice. Sequence analysis of mouse brain RNA done seven weeks later revealed mainly alpha-proteobacteria. Transfer of the bacteria was not observed after heat-treatment of the brain homogenate.

Some viral sequences were also detected in human brain samples. Human herpesvirus-6, Epstein-Barr virus, cytomegalovirus, and coronavirus nucleic acids were detected in some but not all patient samples, while varicella-zoster virus, herpes simple virus type 1, and Saffold virus were not detected in any specimens.

The presence of bacteria in human brain, regardless of underlying disease process, is remarkable. One explanation for this finding might be that soon after death, bacteria invade the brain. This scenario seems unlikely as the findings indicate that the bacteria present in the human brain do not appear to be derived from other body sites. Some of the many questions that come to mind include: Are brain bacteria beneficial, like other components of our microbiome? Is the brain microbiome present at birth or acquired? Do alterations of the brain microbiome lead to human neurological diseases?

We discussed this seminal paper on episode #58 of the science show This Week in Microbiology. Listen to this episode at microbeworld.org and hear our amazement as the story unfolds.

TWiV 204: M m m my corona

On episode #204 of the science show This Week in Virology, Vincent, Alan, Matt and Kathy review isolation of a new coronavirus from two patients in the Middle East, and expansion of the enteric virome during simian AIDS.

You can find TWiV #204 at www.microbe.tv/twiv.

TWiM 30: Unraveling melioidosis and insulin resistance

On episode #30 of the science show This Week in Microbiology, Vincent, Elio, and Michael review how a toxin from Burkholderia pseudomallei inhibits protein synthesis, and the role of the gut microbiome in modulating insulin resistance in mice lacking an innate immune sensor.

You can find TWiM #30 at microbeworld.org/twim.

TWiV 139: Honey, I shrunk the virus

mimivirusHosts: Vincent Racaniello, Alan Dove, and Dickson Despommier

Vincent, Alan, and Dickson discuss the reduction in genome size of Mimivirus upon passage in amoeba, and analysis of the microbiome of honeybees.

Click the arrow above to play, or right-click to download TWiV #139 (96 MB .mp3, 80 minutes).

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Weekly Science Picks

Alan – Life Before the Dinosaurs by ABC
Dickson – Inside Jokes by Matthew M. Hurley
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Listener Pick of the Week

Lance – A History of the World since 9/11 by Dominic Streatfeild

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