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Archive - Aug 30, 2014

Rabies Virus Binds p75NTR to Hijack and Speed Up Transport Machinery in Nerve Cells

Rabies (and rabies virus, its causative agent) is usually transmitted through the bite of an infected animal into muscle tissue of the new host. From there, the virus travels all the way to the brain, where it multiplies and causes the usually fatal disease. An article published online on August 28, 2014 in the open-access journal PLOS Pathogens sheds light on how the virus hijacks the transport system in nerve cells to reach the brain with maximal speed and efficiency. Pathogens that travel in the blood can spread throughout the body without much effort, courtesy of the heart's pumping action. Those traveling outside the blood stream and needing to cover large distances—like rabies virus which depends on the nerve cell network—need to utilize other means of transport. Nerve cells (or neurons) in the periphery, i.e., at the outskirts of the body, as opposed to the central nervous system or CNS), are highly asymmetric: they have a cell body from which a long protrusion called an axon extends to another nerve cell or a target organ like muscle, along a specific transmission route. Axons can measure several hundred times the diameter of the cell body, and, in addition to rapid transmission of electric impulses, they also transport molecular materials over these distances. Rabies virus is known to somehow use this transport system, and Dr. Eran Perlson, from Tel Aviv University, Israel, and colleagues set out to examine the details of how this occurs. The researchers set up a system to grow asymmetric nerve cells in an observation chamber and use live cell imaging to track how rabies virus particles are transported along the axons. The team focused on the p75NTR receptor, a protein which is found on the tips of peripheral neurons and is known to bind a small molecule called NGF (for nerve growth factor).

Early Negative Effects of HIV in Gut May Be Mitigated by Probiotic

Researchers at the University of California at Davis (UC Davis) have made some surprising discoveries about the body's initial responses to HIV infection. Studying simian immunodeficiency virus (SIV), the team found that specialized cells in the intestine called Paneth cells are early responders to viral invasion and are the source of gut inflammation by producing a cytokine called interleukin-1 beta (IL-1 beta). Though aimed at the presence of virus, IL-1 beta causes breakdown of the gut epithelium that normally provides a barrier to protect the body against pathogens. Importantly, this occurs prior to the widespread viral infection and immune cell killing. But in an interesting twist, a beneficial bacterium, Lactobacillus plantarum, helps mitigate the virus-induced inflammatory response and protects the gut epithelial barrier. This study was published online on August 28, 2014 in an open-access article in the journal PLoS Pathogens. One of the biggest obstacles to complete viral eradication and immune recovery is the stable HIV reservoir in the gut. There is very little information about the early viral invasion and the establishment of the gut reservoir. "We want to understand what enables the virus to invade the gut, cause inflammation, and kill the immune cells," said Dr. Satya Dandekar, lead author of the study and chair of the Department of Medical Microbiology and Immunology at UC Davis. "Our study has identified Paneth cells as initial virus sensors in the gut that may induce early gut inflammation, cause tissue damage and help spread the viral infection. Our findings provide potential targets and new biomarkers for intervening or blocking early spread of viral infection," she said.

Proteasome Protection May Be Clue to Unusual Longevity of the Naked Mole Rat

Scientists at the Barshop Institute for Longevity and Aging Studies, part of the School of Medicine at the University of Texas (UT) Health Science Center at San Antonio, have found another secret of longevity in the tissues of the longest-lived rodent, the naked mole rat. They reported that a factor in the cells of naked mole rats protects and alters the activity of the proteasome, a garbage disposer for damaged and obsolete proteins. The factor also protects proteasome function in human, mouse, and yeast cells when challenged with various proteasome poisons, studies showed. These proteasomes usually rapidly stop functioning when poisoned, leading to the accumulation of damaged proteins that further impair cell function, contributing to the vicious cycle that leads to cell death. "I think this factor is part of an overall process or mechanism by which naked mole rats maintain their protein quality," the study’s first author Karl Rodriguez, Ph.D., said. This finding was reported online on July 10, 2014 in the journal Biochimica et Biophysica Acta (BBA): Molecular Basis of Disease. Generally, as an organism ages, not only are there more damaged proteins in need of disposal, but the proteasome itself becomes damaged and less efficient in clearing out the damaged proteins. As a result, protein quality declines and this contributes to the functional declines seen during aging. Enhancement of protein quality, meanwhile, leads to longer life in yeast, worms, fruit flies, and naked mole rats, Dr. Rodriguez said. Dr. Rodriguez, a San Antonio native who completed both his master's and doctoral degrees at the Health Science Center, is a postdoctoral fellow in the laboratory of Rochelle Buffenstein, Ph.D., professor of physiology at the Barshop Institute.