Some Viruses Elicit Immune Response Before Entering Cell; Suburban Sprawl Could Increase Lyme Disease Infections; Human Pediatric Anesthetics Damage Murine Model Brains

In Brief Courtesy of The Bradford Laboratory, University of Helsinki, Finland Some Viruses Elicit Immune Response Before Entering Cell Human cytomegalovirus triggers an immune response before it actually enters the cell, according to a report from researchers at the University of Wisconsin-Madison and the University of Massachusetts (T. Compton et al., "Human cytomegalovirus activates inflammatory cytokine responses via CD14 and toll-like receptor 2," J Virol, in press). The immune system is activated when the virus comes into contact with toll-like receptors on the cell. "No one knew ... that was even possible," says Teresa Compton, associate professor of oncology at Wisconsin. "People thought the virus actually had to get into the cell and start doing its business before the host knew it was there." Three other viruses (respiratory syncytial, murine mammary tumor, and measles) also trigger the immune system when they come into contact with the toll-like receptors. "It may be this is a common molecular trigger," says Compton. "We're trying to understand the specific molecular trigger--what does this alarm system recognize on all these viruses that triggers its activation response," she says. Compton also wants to see if other herpes viruses also trigger toll-like receptors. Understanding this interaction, she notes, would give vaccine makers a better picture of the way the virus triggers the immune system. --Harvey Black Courtesy of Scott Bauer Suburban Sprawl Could Increase Lyme Disease Infections A recent study suggests that suburban sprawl leading to forest fragmentation could also increase the prevalence of ixodid ticks infected with Borrelia burgdorferi, the spirochaete bacterium that causes Lyme disease (K. LoGiudice et al., "The ecology of infectious disease: Effects of host diversity and community composition on Lyme disease risk," Proc Nat Acad Sci, 100:567-71, Jan. 21, 2003). Ixodid ticks become infected as nymphs by taking a blood meal from an infected animal, especially from the white-footed mouse, Peromyscus leucopus. To devise a model for the presence of Borrelia-infected ticks, the researchers sampled bird and mammalian hosts, counting how many blood-engorged tick larvae fell off each animal. They then determined how many larvae were infected. Using these and other data, researchers constructed a mathematical model of the effects of biodiversity on tick infestations. The model suggests that in habitats where there are more potential species of tick hosts, tick larvae are less likely to become infected because some of these hosts have low-reservoir competence; that is, even if bitten by an infected tick, the species either is unlikely to become infected or unable to pass on the infection. "Forest fragmentation," the authors noted, "decreases mammalian biodiversity and results in areas of very high mouse density." Kathleen LoGiudice of Union College in Schenectady, NY, says "sprawling development ... may be increasing our exposure to Lyme and similar vector-borne diseases. Biodiversity can have some very real implications for our health and quality of life." --Myrna E. Watanabe Erica P. Johnson Human Pediatric Anesthetics Damage Murine Model Brains Researchers from the University of Virginia and Washington University, St. Louis, found that a combination of drugs used as pediatric anesthetics results in brain damage and long-term learning and memory disturbances in murine models (V. Jevtovic-Todorovic et al., "Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits," J Neurosci, 23:876-82, Feb. 1, 2003). The investigators researched the effects of a common anesthetic cocktail composed of midazolam, nitrous oxide, and isoflurane. Widespread apoptotic neurodegeneration was observed in many brain regions, including the hippocampus, which is involved in learning and memory. During brain development, when neurons are most susceptible to environmental changes, glutamate allows for proper differentiation, migration, and synapse formation, so neurons can make all the connections needed to function properly. The anesthetics either increase the inhibitory effects of g-amino butyric acid (GABA), the brain's primary inhibitory transmitter, or block glutamate receptors, which would promote cell suicide. Vesna Jevtovic-Todorovic, University of Virginia, associate professor of anesthesiology, says that when synaptogenesis is prevented, neurons disintegrate by apoptosis to let others flourish. "It's kind of like pruning a tree." It is not known yet how these findings will translate to human models. The researchers documented no changes in behavior caused by exposure to the cocktail; however, Todorovic advises against exposing children to these anesthetics. --Hal Cohen

Some Viruses Elicit Immune Response Before Entering Cell; Suburban Sprawl Could Increase Lyme Disease Infections; Human Pediatric Anesthetics Damage Murine Model Brains

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Courtesy of The Bradford Laboratory, University of Helsinki, Finland