Four years from now, in 1999, virologists in the U.S. and Russia willexecute the verdict of the World Health Organization by destroyingthe last two living cultures of smallpox virus.
That final eradication of Orthopoxvirus will leave only one survivingmember of the Poxviridae family that specifically infects humanbeings.
Some dermatologist long ago is said to have christened this poxvirusMolluscum contagiosum (MC) because in its peculiar skin lesions hesaw a fancied resemblance to clamshells.
Unlike its distant genomic cousin, Orthopoxvirus virus, M.contagiosum is not life threatening, but in people with severedepressed immune systems it can be life blighting.
Originally, dermatologists classified MC as a childhood disease, withsolid, smooth, wart-like bumps erupting on the body, presumablycontracted by skin-to-skin contact.
In the 1970s and 1980s, adults began coming to dermatology officeswith the small flesh-colored papules on groin and genitalia,apparently sexually transmitted.
These poxvirus infections, like the childhood ones, were indolent;dispatched spontaneously in several months to a year by the body'simmune defenses. These lesions yield to surgical excision,cryotherapy, chemical ablation or ultraviolet treatment.
Then came HIV.
The year 1983 brought the first two patients with advanced AIDS toreceive a diagnosis, post mortem, of molluscum contagiosum. Theirlesions were far more numerous, and more widely disseminated overthe body. And MC soon joined the list of HIV-related infections _notably Pneumocystis carinii, cytomegalovirus and Kaposi'ssarcoma.
Clinical and research dermatologist Patricia Myskowski of MemorialSloan-Kettering Cancer Center in New York early followed up on theprevalence of MC in HIV patients.
"When AIDS came along," she told BioWorld Today, "we started tosee molluscum as a real problem. On the face, it can be quitedisfiguring."
Myskowski pioneered in relating the extent of MC papules to thedecline of CD4 counts as a patient's HIV progressed to AIDS. "Iguess we were the first people to show," she said, "that the number oflesions you get is inversely proportional to your CD4 count.
Success Of AIDS Drugs Adds To Pox Problem
"People are terribly afflicted when their counts go below 50," sheadded, "but as AIDS patients are living longer, thanks to new drugtherapies, MC is becoming more and more of a problem." In adultswhose HIV-antibody status is unknown, Myskowski suggested, "MCmay be the first indication of HIV infection.
"Conventional treatment," Myskowski pointed out, "which is okay inhealthy people, doesn't work well in patients with HIV, probablybecause the poxvirus that causes these growths is prevalent on theskin far beyond where you can see them.
"So despite the different ways that one treats the papules," sheexplained, "such as scooping or cutting them off, or burning orapplying acids or freezing, the infection comes right back. And thenthe patient can be left with scarring or painful secondary lesions fromthe treatment."
The smooth, flesh-colored MC bumps, dome-shaped with a dimple inthe middle, range in diameter from three to five millimeters. But inadvanced cases proliferating protuberances may merge into giantnodules 1.5 centimeters or more across.
The lesions, Myskowski said, "consist of thickened epidermis, insideof which are a group of virally infected epidermal cells calledmolluscum bodies. These probably shed virus onto the skin surface,"she added, "because viral particles have been found on skin thatapparently does not have a molluscum as yet."
Among the many things that nobody yet knows about M.contagiosum is why it has a predilection for facial sites of eruption."Some people think that shaving makes things worse," Myskowskiobserved. "The tendency is more in the beard area, which tends to bethe worst involved. Mainly men are infected."
But the greatest area of ignorance remains how the poxvirusmaneuvers to evade its human host's immune defenses. A seminalpaper in the latest Science, dated Aug. 9, 1996, narrows this area. Itstitle tells how: "Genome sequence of a human tumorigenic poxvirus:Prediction of specific host response-evasion genes."
The paper's senior author is virologist Bernard Moss, chief of theLaboratory of Viral Diseases at the National Institute of Allergy andInfectious Diseases (NIAID) in Bethesda, Md.
"We don't know the viral strategy yet," Moss told BioWorld Today;"we've just gotten some insights into it." His paper is the first toreport sequencing MC's entire 190,289-base pair genome.
Moss surmised the virus deploys two types of immunity-fightingstrategies: "One is that, unlike smallpox virus, it does not spread intothe bloodstream throughout the body, but stays in the epidermis. Andthat probably minimizes the immune response."
He continued: "In addition, we saw that the virus has certain genesthat suggest they may also prevent an immune response. One of theseis a homologue [has sequence similarity] to MHC, the majorhistocompatibility complex class I molecule."
Moss explained: "This molecule's job is to bring immunogenicpeptides that are derived from viruses onto the surface of the infectedcell, so that lymphocytes are able to recognize that there's a virusinside the cell, and take immune countermeasures."
Diagnostics, Therapeutics Seen As Pay-Off
He and his co-authors "predict that the viral protein inhibits theability of the T lymphocyte to carry out this function."
Moss's laboratory now is testing this premise that the MC poxvirushas a molecule that inhibits the function of MHC, and so interfereswith this normal immune-defense process. They are expressing theviral protein in cultured cells, "and will look directly to see whetheror not it inhibits the normal presentation of antigens."
The "new insights" from sequencing the complete MC genome willpay off in potential aids to diagnosis and therapy, Moss suggested.
"It should now be possible to make a diagnostic assay," he said. "Thevirus is not able to grow in tissue culture, so there's no viral materialavailable to make an assay kit. But we could now express some of itsprotein in host cells of, say, Baculovirus or Escherichia coli. And thatprotein could then serve for an immunological test, to see if peoplehave antibodies to it."
As for a therapeutic drug against MC, "There the strategy could be toexpress the enzymes encoded by the virus, to see whether inhibitorswould affect them. We are starting that work." n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.