Fourteen horses and one horse trainer are dead in Australia, victimsof a newly emerged virus.
Australian virologists describe this hitherto unknown pathogen as amorbillivirus. Their genetic analysis shows it is "distantly related tothe classic morbilliviruses rinderpest, measles and canine distemper."
Their account of this sudden fatal viral onslaught, and how theytracked it down in a week, appears in today's Science (dated April 7),titled "A morbillivirus that caused fatal disease in horses andhumans."
Calling it "classic" is no overstatement. The great Persian physicianRhazes described measles just over a millennium ago in his still-classic work, De Variolis et Morbillis _ "On the Small Pox andMeasles."
Since that 10th-century treatise, a novel type of human morbillivirushad not raised its head until late September of last year. That waswhen 21 horses on a Brisbane horse farm came down with acuterespiratory disease, and 14 died. A few days later, their trainer, 49-year-old Vic Rail, after six days in intensive care, also succumbed tothe mysterious malady. Autopsy revealed severe interstitialpneumonia as the immediate cause of death. His kidney cells hadformed syncytia, a cellular merger typical of morbillivirus.
A 40-year-old stable hand became critically ill but recovered.
Veterinary immunologist Keith Murray, first author of the Sciencereport, heads the Animal Health Laboratory of the CommonwealthScientific and Industrial Research Organization near Melbourne. OnSept. 22, 1994, tissue samples from the dead horses reached hislaboratory, with cause of death "unknown."
Government Declares Highest-Level Alert
At that point, as Science reporter Rachel Nowak wrote in anaccompanying account, the country's Consultative Committee onExotic Animal Diseases imposed a nationwide highest-emergencyalert.
Four days later, the trainer died, and by three days after that Murray'steam, on the basis of RNA analysis, could label the anonymousmicroorganism "equine morbillivirus (EM)." They confirmed that ithad killed Rail too, by recovering the virus from his kidneys.
They assigned EM "to the genus Morbillivirus within the familyParamyxoviridae," which causes mumps and parainfluenza inhumans.
Then, with an antibody test they put together, Murray's peoplescreened 2,500 horses and 90 humans in the neighborhood of theBrisbane outbreak. Finding none infected, they declared themorbillivirus emergency over.
Emergent viruses are all the rage these days. Richard Preston's book,The Hot Zone, which describes the recent discovery of the lethalEbola and Marburg viruses, has been on the New York Times non-fiction best-seller list for 25 weeks, where it remains today numbertwo.
Like the 1993 hantavirus flare-up in the American southwest (seeBioWorld Today, Dec. 13, 1994; p. 1) viruses tend to attack humansfrom their jumping-off place in lesser mammals. Hantavirus's naturalhost turned out to be a rodent, the deer-mouse. African monkeysincubate the Marburg and Ebola killers, and are the usual suspects ofHIV.
In fact, in early October, Murray sent sera from the dead horses andtrainer to his former mentor, virologist Brian Mahy, who heads theDivision of Viral and Rickettsial Diseases at the U.S. Centers forDisease Control and Prevention (CDC) in Atlanta. "At the time theincident occurred, Mahy told BioWorld Today, "there was concernthat the respiratory illness might actually be hantavirus pulmonarysyndrome, such as we see in the southwest. We found a negative."
He added that Murray will be giving a talk at CDC next Thursday,and "Hopefully, we'll be able to set up some collaboration on thisissue."
Hunt On For Animal Reservoir
Now Australian veterinarians are planning to collect blood fromevery species of animal in the Brisbane suburb of Cannon Hill, wherethe first horses got infected. Murray's lab will test these samples forEM in an attempt to identify, and thus control, EM's animalreservoir.
Should this effort fail, Nowak pointed out, "The fear is that if EMnaturally infects livestock, Australia's meat and livestock industrywould be destroyed as other countries ban imports."
It was electron microscopy plus the tools of biotechnology that madeit possible for Murray's team to detect, identify and name EM in ascant week.
Initially, to confirm suspected viral etiology, spleen and lunghomogenates from the infected horses were inoculated andinsufflated into two healthy horses. At the same time, postmortemtissue samples from the deceased human victim went into cellcultures.
The two recipient horses developed signs of infection within six and10 days, respectively, when they were put down. Samples of theirtissues were passaged into two more animals, which contractedterminal disease by four and five days.
Electron microscopy identified herringbone-shape viralnucleocapsids in all four experimental horses, and in virions re-isolated from their visceral organs. These all displayed the telltalesyncytial giant cells of morbillivirus. One unique feature of EM wasits "double-fringed" appearance, reflecting two disparate sets ofsurface projections, 10 and 18 nanometers long, studding the viralenvelope.
Immunologists on the team then tested the virus against serumsamples containing antibodies against a range of presumably relatedviruses. Immunofluorescence and protein immunoblot analysesrevealed a very weak reaction in rinderpest, a scourge of cattle inAfrica.
Comparative sequence analysis of a portion of EM's matrix proteingene confirmed its membership in the Morbillivirus genus.Polymerase chain reaction (PCR) primers amplified specific stretchesof that gene, from affected equine and human tissues, and tested fortheir capacity to initiate DNA synthesis in PCRs.
As for the apparent subsidence of the viral threat, Mahy said, "Thatthere is no evidence of any continuing activity by what appears to bea new and extremely interesting virus makes it all the moreintriguing, of course." n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.