Some brain cells are better virus fighters

Viruses often spread through the brain in patchwork patterns, infecting some cells but missing others. New research at Washington University School of Medicine in St. Louis helps explain why. The scientists showed that natural immune defenses that resist viral infection are turned on in some brain cells but switched off in others.

“The cells that a pathogen infects can be a major determinant of the seriousness of brain infections,” says senior author Michael Diamond, MD, PhD, professor of medicine. “To understand the basis of disease, it is important to understand which brain regions are more susceptible and why.”

While some brain infections are caused by bacteria, fungi or parasites, often the cause is a virus, such as West Nile virus, herpesvirus or enteroviruses.

For their study, now available online in Nature Medicine, the researchers focused on granule cell neurons, a cell type that rarely becomes infected. They compared gene profiles in granule cells from the cerebellum with the activity in cortical neurons in the cerebral cortex, which are more vulnerable to infection.

The comparison revealed many differences, including a number of genes in cortical neurons that were less well-expressed—meaning that for those specific genes there were fewer copies of mRNA, the molecules that relay genetic information from DNA to the cell’s protein-making mechanisms.

Next, the researchers transferred individually 40 of those genes into cortical neurons and screened the cells for susceptibility to viral infection. The test highlighted three antiviral genes that are induced by interferon, an important immune system protein. When the expression level of these genes increased in cortical neurons, the cells’ susceptibility to viral infection decreased.

The researchers also identified mechanisms that make some of these changes in genetic programming happen: regulatory factors known as microRNA, and differences in the way DNA is modified in the cell nucleus, both of which can affect gene expression levels.

Some of the genetic changes are only helpful against specific viral families, while others are effective against a broader spectrum of viruses and bacteria. The scientists can’t say yet if the differences in infection susceptibility are driven by the need to prevent infection or if they are a byproduct of changes that help neurons in particular brain regions perform essential functions.

To learn more about how these innate immune genes help cells resist infection, Diamond and his colleagues are disabling them in the brains of mice.

Temple scientists find cancer-causing virus in the brain, potential connection to epilepsy

Researchers at Shriner’s Hospital Pediatric Research Center at the Temple University School of Medicine, and the University of Pennsylvania have evidence linking the human papillomavirus 16 (HPV16) – the most common cause of cervical cancer – to a common form of childhood epilepsy. They have shown for the first time that HPV16 may be present in the human brain, and found that when they added a viral protein to the brains of fetal mice, the mice all demonstrated the same developmental problems in the cerebral cortex associated with this type of epilepsy, called focal cortical dysplasia type IIB (FCDIIB). The findings suggest that the virus could play a role in the development of epilepsy.

The results also mean that doctors may have to re-think their approach to treating this type of epilepsy, and perhaps consider other therapeutic options related to HPV, an infectious disease.

"This is a novel mechanism, and it fills a gap in our understanding about the development of congenital brain malformations," said Peter Crino, MD, PhD, Professor of Neurology at Temple University School of Medicine, and a member of Shriner’s Hospital Pediatric Research Center, and the senior author of a recent report in the Annals of Neurology.

"If our data are correct, future treatment of cortical dysplasia could include targeted therapy against HPV16 infection, with the goal of halting seizures. Identifying an infectious agent as part of the pathogenesis of brain malformations could open up an array of new therapeutic approaches against various forms of epilepsy."

(Image: ASME.org)

Bioengineers Introduce ‘Bi-Fi’ — The Biological ‘Internet’

If you were a bacterium, the virus M13 might seem innocuous enough. It insinuates more than it invades, setting up shop like a freeloading houseguest, not a killer. Once inside it makes itself at home, eating your food, texting indiscriminately. Recently, however, bioengineers at Stanford University have given M13 a bit of a makeover.

The researchers, Monica Ortiz, a doctoral candidate in bioengineering, and Drew Endy, PhD, an assistant professor of bioengineering, have parasitized the parasite and harnessed M13’s key attributes — its non-lethality and its ability to package and broadcast arbitrary DNA strands — to create what might be termed the biological Internet, or “Bi-Fi.” Their findings were published online Sept. 7 in the Journal of Biological Engineering

Using the virus, Ortiz and Endy have created a biological mechanism to send genetic messages from cell to cell. The system greatly increases the complexity and amount of data that can be communicated between cells and could lead to greater control of biological functions within cell communities. The advance could prove a boon to bioengineers looking to create complex, multicellular communities that work in concert to accomplish important biological functions.

Confirming earlier scientific doubts, a new study concludes that chronic fatigue syndrome is not caused by two viruses known as XMRV and pMLV.

Researchers from the U.S. National Institutes of Health, the U.S. Centers for Disease Control and Prevention, Columbia University and other institutions, including some scientists who did the original research, examined 147 patients with chronic fatigue syndrome from sites across the country and compared them to 146 healthy patients.

Bottom line? “This analysis reveals no evidence of either XMRV or pMLV infection,” the authors wrote. The study is published in the September/October issue of the journal mBio.

The UT Dallas “tag and track” method not only sheds light on how DNA loops form, but also might be adapted to screen drugs for effectiveness against certain viruses that shuffle genetic material, such as HIV.

Until now, scientists primarily had “snapshots” of the initial and final stages of DNA loop formation, with only limited information about what happens during the intermediate steps.

"Scientists have known for more than 30 years that DNA looping is an important part of molecular biology and gene regulation, but until our work, there have been few serious attempts to understand the basic biophysics of the process, … We estimate that using fluorescence-based methods such as this for drug screening could be as much as 10,000 times more efficient than methods that are currently used," -Dr. Stephen Levene, professor of bioengineering, molecular and cell biology, and phyiscs at UT Dallas.