By David N. Leff
Another count has been added to the indictment of El Nino — the periodic climate-skewing mass of warm water in the Pacific Ocean.
"People are very worried this year," said virologist Stuart Nichol, "about a fresh epidemicof hantavirus pulmonary syndrome, such as we saw back in 1993, when the hantavirus wasfirst identified.
"In this El Nino year," Nichol told BioWorld Today, "people are concerned thatrodent populations are on the rise in the Southwestern U.S. because of the mild springconditions."
Nichol is chief of molecular biology in the special pathogens branch at the Centers forDisease Control (CDC), in Atlanta. He had a leading hand in linking the newly discoveredvirus to its rodent vectors in the Southwestern U.S. (See BioWorld Today, Nov.5, 1993, p. 1, and Dec. 13, 1994, p. 1.)
"Rodent dynamics feature tremendous increases in mouse populations, followed bytremendous crashes," he pointed out. "These are reflected in peaks and valleys of peoplebecoming infected with the virus, and identification of hantavirus pulmonary syndrome(HPS) cases. But so far at least," Nichol added, "we've not seen any indication that wehave a fresh epidemic of HPS this year, as we did see back in '93."
Hantavirus Now In 29 States
That hantavirus debut, which started in New Mexico and Arizona, has now spread to 29states. "In that area," said CDC medical epidemiologist Aly Khan, "183 cases have beenconfirmed since 1993. But the first-ever identified patient goes back retrospectively to1959. In addition, another 50 cases have been identified after the fact up to 1993," Khantold BioWorld Today, "and most of them are dead.
"That leaves 132," he continued, "with an overall fatality rate of 44 percent in '93. Butsince January 1, 1994, that rate is down to 33 percent."
Khan also cited 24 cases in Canada, and 178 in five South American countries.
A large part of hantavirus's deadliness is its innocuous onset.
"Diagnosis is part of the problem," Nichol observed. "By the time a patient presents tohospital, death may be only a matter of days away. A general flu-like illness can veryrapidly progress to filling up the air spaces of both lungs with fluid. The victim literallydrowns in his own bodily fluid, mostly water from the blood's serum."
This leakage takes place because the junctions that form seamless boundaries between theendothelial cells of lung and blood vessel open up. "What pries them apart," Nicholpointed out, "is an area of very active research. We don't know."
The only therapy for HPS is the antiviral ribavirin, he said, "which in tissue culure could beshown to be effective against hantaviruses. There's now a clinical trial, coordinated by theUniversity of New Mexico, in Albuquerque."
A paper in today's issue of the Proceedings of the National Academy of Sciences(PNAS), dated June 9, 1998, makes an exploratory dent in this area of ignorance.Its title: "Beta-3 integrins mediate the cellular entry of hantaviruses that causerespiratory failure." The article's senior author is virologist Erich Mackow, at the StateUniversity of New York, in Stony Brook.
The novel finding in this research, Mackow told BioWorld Today, "is that theentry of hantaviruses into endothelial cells is facilitated by a cell-surface receptor forintegrin, a protein that connects the outside of cells with their interior.
"That entry," Mackow explained, "by means of receptor-mediated endocytosis, is the firststep by which a virus gets into the cell and starts to replicate in the pulmonaryendothelium. This particular integrin receptor, besides facilitating hanta's entry, is involvedin cell-to-cell adhesion, which the virus presumably disrupts. It's using a receptor that'snormally responsible for holding cells together — in other words preventing theleakiness of the endothelium."
Mackow reported that "antibodies to this specific receptor block the ability of the virus toenter those cells. But," he noted, "our antibodies did not block this completely. So we'reinterested in studying that, and figuring out whether there are other receptors." *