All day Tuesday, the event leading the TV news was an outbreak ofEbola virus at a monkey colony in southern Texas.
Twenty television cameras, plus nearly 100 print media reporters,converged on the small town of Alice (pop. 19,000), 50 miles west ofCorpus Christi. There, the HRP Inc. primate quarantine facilityrecently received a shipment of 100 cynomolgus monkeys from asupplier in the Philippines. One animal died on March 30, 1996, ofmultiple internal hemorrhages.
Blood taken from a second monkey, euthanized on Saturday, enabledthe Centers for Disease Control and Prevention (CDC) in Atlanta toconfirm infection by the Reston subtype of Ebola virus.
Tuesday morning, the Texas Department of Health convened a pressbriefing in Alice to update the media on the local outbreak. TexasCommissioner of Health David Smith emphasized, "This is not thesame Ebola subtype that caused the outbreaks in [Zaire] Africa. TheReston virus has never caused serious illness or death in humans."
In a separate interview, CDC virologist Anthony Sanchez toldBioWorld Today, "Whether the Reston subtype is less pathogenic forhumans than the Zaire is unclear. It's very capable of killing monkeysefficiently. Zaire and Reston," he added, "are quite, quite differentsubtypes, yet they belong to the same group of Filoviruses."
CDC research officer Sanchez is a commander in the uniformedPublic Health Service. "These samples from Texas," he said, "werefirst ID'd by tests conducted by the U.S. Army Medical ResearchInstitute for Infectious Diseases at Fort Detrick, Maryland.
"We found out about it late last week," he continued, "and we'vebeen working over the weekend to characterize it. We've confirmedFt. Detrick's finding, using PCR to detect the virus; sequenced theentire glycoprotein gene, and sequences of the nuclear protein andpolymerase genes as well. We found that this virus is approximately99 percent identical to the original Reston."
Reston, Va. is a suburb of Washington, D.C. with a primate colonywhere Ebola erupted in late November 1989.
"It created a big scare," Sanchez recalled, "when they found outthrough the electron microscope that they were dealing with a virus inmonkeys that looked a lot like Ebola _ and there was a panic inReston."
That alarm metastasized to primate colonies in Texas andPennsylvania, the CDC researcher recalled. Both sites had receivedanimals from the same shipment. From their origin with the FerliteScientific Research company in the Philippines, he said, "themonkeys were shipped to Amsterdam, Holland, where the shipmentwas split in two. Half of the animals went to Germany; half to theU.S. We heard all about the cases here, but not a single thing aboutwhat happened in Germany."
Out of Africa, Via The Philippines, Into Virginia
That first Reston Ebola incident, he said, led the FDA to establish aquarantine policy for primate colonies. "When monkeys come intothis country for testing," he observed, "they have to be put into aholding facility for 30 days. They come in, they get bled, they'retested, they're monitored. If one comes up positive, that restarts thequarantine period for everybody."
Ebola was just a river in the central African nation of Zaire until1976, when it gave its name to a previously unknown hemorrhagicvirus that killed 430 (80 percent) of its 550 infected victims in achain reaction of contagion.
In late 1994 and early 1995, Ebola dramatically reemerged in Africa.This time it killed 245 (77 percent) of 316 cases In the Zairian city ofKikwit. Months earlier, it had surfaced in the faraway Ivory Coast,but caused only a single non-fatal human infection. In neighboringGabon, 13 died of the untreatable, unpreventable pathogen.
That was enough, though, to add another acronym to the Ebolavirus's four genetic subtypes: Z for Zaire; S for Sudan (where casesflared in 1977); IC for Ivory Coast; R for Reston.
No two of their gene sequences are alike. "They range," Sanchezobserved, "from about 37 percent to 40 percent nucleotidedifferences, which is quite a bit of difference. It's like comparing,let's say, a tiger to a pussycat. Genetically, they're linked, but one hasa little bit more ability to do damage _ and you might apply that toReston 1996."
By coincidence, the Proceedings of the National Academy ofSciences (PNAS), dated April 15, 1996, carries a paper titled: "Thevirion glycoproteins of Ebola viruses are encoded in two readingframes and are expressed through transcriptional editing." Its firstauthor is Sanchez.
How Can One Gene Make Two Proteins?
"The most unusual finding in that paper," he said, "was that theglycoproteins of all Ebola subtypes are encoded in two readingframes. In each case, a secreted, non-structural glycoprotein waspredicted as the primary gene product, and the structural virion formof the glycoprotein is expressed through transcriptional editing.
"It's a bizarre twist," Sanchez continued, "on a theme described inparamyxoviruses, which cause measles and mumps. Ebola simplyswitches frames by just adding another base, and thereby produces asubstance that may help it in establishing a persistent infection." The"editing" process, consists of a slippage or stutter of the polymerase,whereby the one gene produces two separate protein products.
Sanchez and his co-workers have expressed and identified both ofthese, in collaboration with a university group that has "seendifferences between the two proteins in terms of cellular immuneresponse." He added: "We're not at liberty to discuss that."
His take-home message is, "We can't take for granted the image ofthe gene that we have. It's clear from this work on these RNA virusesthat certain genes can produce more than one product. This issomething that I think will be found out in the future, that multiplegene products will be produced by certain viral _ and human _genes."
Meanwhile, his team is immunizing rabbits and mice with uniquesequences taken from the 1976 Zaire subtype, "because we feel it'sthe most pathogenic Ebola virus, and the first one." Their goal is to"get antibodies that would be useful not only for prevention but fordiagnostic purposes as well." n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.