By David N. Leff
Viruses - especially newly emergent ones - tend to be named after the locality in which they were discovered. Examples: Ebola (East Africa), Lassa (West Africa), Bunyamwera (Uganda), Marburg (Germany), Powassan (Canada), Coxsackie (New York), Sendai (Japan), and of course, West Nile.
But there's one deadly new virus that has no name at all - literally. Rather, its moniker, Sin Nombre, means "no name" in Spanish. In 1993-94 this particular hantavirus struck down more than two dozen people in the Four Corners region where New Mexico, Arizona, Colorado and Utah abut - which is home to tribal residents of the Navajo Indian reservation. (See BioWorld Today, June 9, 1998, p. 1.)
Virologist Brian Hjelle, at the University of New Mexico (UNM), in Albuquerque, tells how Sin Nombre got its no-name name: "I think it was the product of some negotiation between CDC - the Centers for Disease Control - and the Navajo tribe in New Mexico. They felt that by virtue of oral history their medicine men had identified this disease, or this virus, before CDC did. In January 1994, CDC had named it the Muerto Canyon - Canyon of Death - virus," Hjelle recalled, "after a valley in the Navajo Nation near Four Corners. The Indian elders told CDC they were offended by this, because it identified a sacred site. Apparently, they told the agency that the only name they found acceptable was No Name virus. So when CDC objected, someone decided to say it in Spanish."
The viral reservoir that infects humans does have a name - deer mice.
Sin Nombre virus hasn't gone away. Hjelle, an associate professor of pathology at UNM School of Medicine, observed: "At our hospital, we've treated 15 patients so far in the year 2000. Most of them promptly went on extracorporeal membrane oxygenation (ECMO). California has had about seven thus far this year. So there's a lot of cases here. Nationwide, the CDC counts a little over 250, but they're missing probably about 30 from Four Corners.
Nationwide Body Count Pushes 300
"At any given time over the summer," he continued, "we've had two or three cases going. Of 15, a couple of them died. But we've had two who were dead on arrival, one from Colorado, one from Arizona. And another one who was put on ECMO, lasted a day or so and then died. And then another one succumbed recently. ECMO is a high-risk procedure," Hjelle commented. "Extracorporeal membrane oxygenation is essentially a complete heart-lung bypass. Your heart and your lungs can be shut down, and the machine can keep all but the most critically ill alive - maintaining blood pressure until the virus goes away.
"This is a year of La Niqa," Hjelle mused, "when we're really not supposed to have much of the viral infection. So this is also tending to trash the conventional wisdom about El Niqo being the culprit - making the mice go crazy and infect human beings."
Hjelle is senior author of a paper in the latest Proceedings of the National Academy of Sciences (PNAS), dated Sept. 12, 2000. Its title: "Experimental infection model for Sin Nombre hantavirus in the deer mouse (Peromyscus maniculatus)."
"One of the most basic things you need in any kind of pathogen study," he told BioWorld Today, "is an animal model. It's a way to finally address issues of pathogenesis - tissue distribution, immune response, vaccine preparation. It's enabling us to study the ways the deer mouse spreads the virus in nature, what happens when it gets into them, why is doesn't contract symptoms when infected. All these are open questions that are essentially untouchable without animal models."
Hjelle also made the point that the main reason the field hasn't created a murine model of Sin Nombre is because such contagion-fraught work can only be undertaken in a Level 4 biosafety containment facility - at multi-million-dollar cost. He and his co-authors made an end-run around this roadblock by taking their mouse-colony creating outdoors.
"We went up in the mountains," Hjelle recounted, "and trapped the deer mice in the wild. We brought them down, drew blood from them right away and tested it for hantavirus antibodies. The ones that were negative we put in quarantine, at our outdoor lab in the remote Sevilleta Wildlife Refuge. We gave them five weeks, then tested them again. One mouse seroconverted to infectivity, but most of them stayed negative.
"The 69 negatives," he went on, "we brought down to the university and bred. After five weeks, we tested those 69 mice again, and one of them had become positive. The other 68 were all housed in very segregated conditions, so there was no way for them to cross-infect. They went up to the campus and founded a colony. These mice produced around 70 to 90 pups a month. We had 52 pairs initially; now our colony numbers about 300 animals over several generations.
"The mouse that seroconverted," Hjelle related, "we used as source of virus. She also delivered four pups, which is interesting because 19 days after birth they were all antibody-positive, but they didn't have virus - which is the first direct test of vertical transmission done yet. Ultimately, we had the virus and could pass it from mouse to mouse."
Deer mice have nothing to do with deer. They got their name because both animals sport brown coats and white tails." They have a pure white belly and a bi-colored tail," Hjelle observed, "the bottom of which is white and the top dark. They're a shade bigger than regular mice, running up to 20 to 25 grams for an adult. Deer mice have bigger eyes and ears than conventional mice, and are much better-looking."
Vaccinated Deer Mice Show 'Progress'
"In the lab," he went on, "we've got females that have produced 18 or 19 litters. In nature, they tend to give birth twice a year, with 23-day gestation period and five days estrus - although they have the potential to produce much more in appropriate conditions. Spring and fall are typical boom times for deer mice."
For the past year, Hjelle and his team have been testing an anti-Sin Nombre vaccine in their mouse colony, "and now are making progress," Hjelle observed, adding, "The first thing we want to do is show that the vaccine works in deer mice. Then we'd have something out there that could be a candidate for human testing - if a company wanted to step up to the plate." n