Editor’s note: Science Scan is a roundup of recently published biotechnology-relevant research.
For decades, viruses have been indicted on circumstantial evidence as perpetrators of multiple sclerosis (MS), an autoimmune disease. One circumstance: MS is six times as frequent in Winnipeg (125 degrees north latitude) as in New Orleans (30 degrees north). By that same latitudinal rationale, MS is rare between the sun-drenched tropics of Cancer and Capricorn.
How come? It’s a virus, stupid!
The same viral-infection paradigm has long ago reached a different autoimmune disease Type I diabetes, also known as juvenile-onset diabetes. This disorder may have many causes, ranging from autoimmunity to inheritance to infection with enteroviruses, which hang out in the alimentary canal. They include polioviruses and coxsackievirus, a highly infectious pathogen that mimics polio’s symptoms but minus the paralysis. (Coxsackievirus is named for a village in upstate New York.)
Immunologists at the Scripps Research Institute in La Jolla, Calif., are authors of an article in the April issue of Nature Immunology titled: “Target cell prevents the development of diabetes after viral infection.” For openers, they note, “The mechanisms that regulate susceptibility to virus-induced autoimmunity remain undefined.” Their paper “establishes a fundamental link between the responsiveness of target pancreatic beta cells to interferon, and prevention of coxsackievirus-induced diabetes.” (Those beta cells carry the islets of Langerhans, which produce insulin.)
The authors report that “an intact beta-cell response to the interferon’s antiviral defense resulted in a reduced permissiveness to infection and subsequent natural killer cell-dependent death.” They made these findings in mice infected with coxsackievirus. When the murine beta cells were prevented from generating their normal response to interferons, the virus severely damaged those cells. The mice developed an acute form of diabetes resembling the disease that occurs in humans after severe enteroviral infection. They made the point that by responding vigorously to natural antivirals i.e., interferons the animals’ beta cells play an active role in their own survival.
Inoculation of mice with coxsackievirus results in rapid dissemination of the virus to vital organs such as the liver, kidneys, spleen, heart and pancreas. To determine whether INF responsiveness is critical for pancreatic beta-cell survival during a systemic infection with coxsackievirus, the Scripps team generated transgenic NOD (non-obese diabetic) mice that expressed the suppressor of cytokine signaling under the control of the insulin promoter. In wild-type islets, IFN treatment significantly reduced the production of infectious virus. They concluded that “an intact beta-cell response to INF is required to prevent diabetes after a systemic coxsackievirus infection.”
So much for mice.
The journal article observed, “The human coxsackievirus adenovirus receptor protein plays a central role in the productive infection of human pancreatic islet cells.” It added, “Hence, an increased understanding of the molecular mechanisms behind IFN-induced antiviral defenses in pancreatic beta cells could facilitate the development of antiviral therapy that may provide effective prophylaxis for humans with acute-onset of Type I diabetes.” Moreover, “enhanced antiviral defenses may also benefit individuals with a genetic predisposition to develop autoimmune Type I diabetes.”
Prescription For Growing Brain Cells: Swim Two Laps And Call Me In The Morning
It’s old news by now that animals, from birds to folks, can make new neurons in their hippocampus a cerebral center important for learning and memory. But it’s not been clear whether these neophyte nerve cells actually turn into full-fledged functioning members of the brain team. Now a paper in Nature, dated Feb. 28, 2002, sets this uncertainty at rest. Its title: “Functional neurogenesis in the adult hippocampus.” Its authors are geneticists and neurobiologists at the Salk Institute for Biological Studies in La Jolla, Calif.
They report that indeed the new mouse neurons pull their own weight but it takes them four months to reach full steam. To circumvent the handicaps to reaching this finding, the authors used a retroviral vector expressing green fluorescent protein (GFP), a marker that labels only dividing cells, and is visible in live hippocampal slices. “Newly generated cells in the adult mouse hippocampus,” they note, “have neuronal morphology similar to that of mature dentate granule cells.”
They suggest that the newly generated neurons may have a role in cognition and brain repair. “For example,” their paper points out, "manipulations that increase neurogenesis, such as an enriched environment and exercise, are associated with improved memory function. In addition, new neurons are generated in the hippocampus after strokes and seizures, suggesting that they may be involved in recovery from injury.”
Highly Effective Anti-HIV Drug Abacavir/ Ziagen Can Be hazardous To Your Life
From A to Z, abacavir (common name) to Glaxo’s Ziagen (trade name) is a highly effective antiretroviral drug against HIV, the AIDS virus. However, it carries a red warning flag: Patients who include abacavir in their treatment regimen court a statistically minor risk of death by the drug’s life-threatening hypersensitivity in a small proportion of individuals.
A paper in the March 2, 2002, issue of The Lancet carries this foreboding title: “Association between presence of HLA-B*5701, HLA-DR7 and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir.” Its authors are clinical immunologists at Murdoch University in Perth, Australia.
Its lead author, Simon Mallal, commented, “The findings have important clinical implications. In our population, withholding abacavir in patients with this haplotype would be expected to reduce the prevalence of this potentially life-threatening event from 9 percent to 2.5 percent without inappropriately denying the drug to any patients. Based on these data, it is our current practice to withhold abacavir in patients who have the HLA-B*5701, HLA-DR7 and HLA-DQ3 haplotypes. However, before such practice can be taken up by others, it is essential that the association between HLA type and abacavir hypersensitivity in their own populations is assessed.”