Editor's Note: Science Scan is a round-up of recently publishedbiotechnology-related research.
Before 1962, when an attenuated live-virus vaccine against measleswent on line in the U.S., half a million children a year came downwith the infection's dusky-red cheek rash and high fever. Many ofthem died, typically of bacterial pneumonia brought on by themeasles virus.
Since then, routine vaccination at 12 to 15 months of age, oftenfollowed by a booster shot when the child enters kindergarten, hasreduced measles in the U.S. from a common scourge to an occasionalflare-up.
"There's a measles epidemic right now in Quebec," observedvirologist and microbiologist Diane Griffin. "The disease hasn't beenstamped out yet." In Third-World countries, she told BioWorldToday, "the measles virus kills one to two million children a year,most of them from secondary respiratory infections."
Griffin chairs the department of microbiology and immunology atJohns Hopkins University School of Hygiene and Public Health, inBaltimore. She and her colleagues have been in hot pursuit of themeasles virus since the early 1980s, to find out why and how ittriggers the opportunistic infections that do its death-dealing dirtywork.
"We've examined the immune systems of hundreds of kids withmeasles in the past 10 or 15 years," she recalled, "with the purpose oftrying to understand why these children are so highly susceptible tosubsequent bacterial diseases."
Griffin's paper in the current issue of Science, dated July 12, 1996,reports her group's latest discovery: "Mechanism of suppression ofcell-mediated immunity by measles virus."
She and her co-authors found a new and telling role for a cell-membrane molecule known as CD46.
Besides being the measles virus cell receptor, CD46 turns on thecomplement signal that triggers immune-system monocytes andmacrophages to consume invading pathogens.
"Nobody knew before us," Griffin said, "that binding CD46 modifiedthe immune function of monocytes _ namely, their production ofinterleukin-12 [IL-12]."
Operating through its CD46-to-complement chain of command, theHopkins group determined, measles virus wipes out interleukin-12, apotent cytokine, which hustles key components of the CMI defensesto their action stations.
This discovery was derived from the analysis of human white bloodcells infected in vivo by wild-type measles virus. "Now," Griffin said,"we're going after monocytes from measles patients, to make surethis is what really happens in people."
Synaptic, Ciba-Geigy Discover CrucialAppetite-Regulating Receptor In Brain
First there was leptin, acclaimed as a putative slimming drug. AmgenInc., of Thousand Oaks, Calif., has recombinant leptin in Phase Ihuman trials.
Then came neuropeptide Y (NPY), a major stimulant to feedingbehavior. Biochemist Richard Palmiter at the University ofWashington, Seattle, made transgenic mice missing the gene forNPY, but bemoaned the lack of a pharmacological antagonist to theeat-more molecule. (See BioWorld Today, June 6, 1996, p. 1.)
Now Synaptic Pharmaceutical Corp., of Paramus, N.J., announcesdiscovery of "A receptor subtype involved in neuropeptide Y-induced food intake." That's the title of its paper in the current issueof Nature, dated July 11, 1996.
Together with Ciba-Geigy Ltd. of Basel, Switzerland, its research anddevelopment partner, Synaptic reports the expression cloning of anNPY-type receptor from rat hypothalamus. Centers of that brainregion are linked to feeding and "regulating the emotive aspect ofappetitive behaviors."
This leads the co-authors to theorize that their newly cloned cerebralmolecule may be the long-sought "feeding receptor." If so, drugs thatblock it could offer new treatments for obesity _ a lead that Ciba-Geigy's Metabolic Risk Factor department is avidly pursuing.
Rabies Virus Gets High Marks As Vector;Vesicular Stomatitis Virus Even Higher
A team of veterinary molecular biologists in TYbingen, Germany, ispredicting "the successful future use of recombinant rhabdovirusvectors for displaying foreign antigens or delivering therapeuticgenes."
Their research paper in the current Proceedings of the NationalAcademy of Sciences (PNAS), dated July 9, 1996, reports thisprediction under the title: "Highly stable expression of a foreign genefrom rabies virus vectors." The article describes how they generated achimeric negative-strand rabies virus that expresses a foreign protein,the bacterial chloramphenicol acetyltransferase (CAT) gene. "CATactivity," they note, "was still observed in cell cultures infected withviruses passaged for more than 25 times."
Postdoctoral fellow Matthias Schnell, now on a two-year fellowshipin the pathology department of Yale University School of Medicine,explains the superiority of rabies virus over more conventional genedelivery vectors: "Rabies is so stable," he told BioWorld Today; "itdoes not integrate into the genome. That's a big advantage." Headded, "It's more for transient expression in immunization than forgene therapy."
Schnell now has trumped rabies' ace with what he describes as a stillmore efficient vector, recombinant vesicular stomatitis virus (VSV).
"VSV," he said, "has an incredibly high titer. Rabies' final titer is108; VSV's, 109 or even 1010.
In the laboratory of Yale pathologist Jack Rose, Schnell is "actuallyworking on expressing human CD4, in VSV. We got incorporation ofthis CD4 in the virion, and are now trying to use that as a receptor toinfect HIV-infected cells. Normally gp 160 docks with the CD4receptor; now we try it the other way around _ getting gp160 to dockwith the CD4 virus-expressing cells. That may be a nice method tokill HIV-infected cells." n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.