By David N. Leff
Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.
So far, virologists have identified five persuasions of hepatitis virus that infect humans - A, B, C, D, E - and still counting. Hepatitis B virus (HBV) is by far the most deadly; it ranks as the ninth leading infectious killer worldwide.
In the U.S. alone, half a million people a year come down with HBV, which they catch through exposure to infected blood, semen, vaginal fluids and saliva. It kills by attacking the liver with chronic inflammation, cirrhosis and hepatocellular carcinoma. (See BioWorld Today, Feb, 18, 2000, p. 1.; and Feb. 22, 2000, p. 1.)
Other mammalian versions of hepatitis B virus are rife in a wide variety of wild fauna - notably, squirrels, birds and chimpanzees. Soon after discovery of human HBV a quarter-century ago, it turned out that captive chimps in primate centers - the primary laboratory animal model of HBV infection - could acquire the infection from experimental injections of the human virus. Even wild-caught chimpanzees, out of Africa, proved positive for the HBV surface antigen - evidence they had been infected.
But virologists questioned whether these animals contracted the infection on their own. Rather, they surmised, they had picked up the human virus because, when captured, they received injections of human serum to improve their chances of survival during transportation to ultimate destinations. The scientists suspected that that serum came from the more than 10 percent of Africans infected with chronic HBV.
In the last few years, however, new evidence from other non-human primates suggested that they were infected with indigenous non-human virus. To confirm the existence of a chimpanzee-specific HBV strain, virologists at the Centers for Disease Control (CDC) and National Institute for Allergy & Infectious Diseases (NIAID) checked out the genetic relatedness of viral isolates from 13 infected chimps. Eleven of them had been caught wild as babies, before chimpanzees joined the list of threatened species.
Their findings appear in the Proceedings of the National Academy of Sciences (PNAS) dated Feb. 15, 2000, bearing the title: "Identification of hepatitis B virus indigenous to chimpanzees."
The co-authors identified a unique chimp HBV strain in 11 of the 13 animals, based on nucleotide and amino acid analysis of the complete viral genome, and the gene encoding its surface antigen. This data indicated that chimpanzee HBV is distinct from known human forms of the virus, but genomically is akin to virus isolated from Old World great apes - gibbons, gorillas and orangutans - and New World monkeys.
Their PNAS article cautions that because human HBV causes disease in chimps, "the potential for zoonotic disease transmission exists where blood or body fluid exposure is common - as in animals kept as family pets, or situations in which they are slaughtered for bushmeat." It conclude that "available hepatitis B vaccines would prevent infection in the unlikely event of exposure to non-human primate HBVs."
Chimpanzees (Pan troglodytes) are the closest mammalian relatives to humans (Homo sapiens), with genomic similarity pushing 99 percent.
Linking Human, Rodent Cells Unmasked Mutations Normal Chromosomal Allele Hid
Like shoes, gloves, lungs and kidneys, all human chromosomes come in pairs - except for the haploid X and Y sex-determination chromosomes. We inherit one of these paired bundles of DNA - called alleles - from paternal parent, the other from maternal. This diploidy has great genetic advantages, but it sometimes gums up the works of genomic analysis.
The problem is that mutations in one allele can be covered up by the other. A paper in Nature dated Feb.17, 2000, reports a method that solved this hang-up in genetic testing for colorectal cancer. Its title: "Conversion of diploidy to haploidy: Individuals susceptible to multigene disorders may now be spotted more easily." This "conversion" approach fused human and rodent cells to create hybrids containing only a targeted subset of the human karyotype. The co-authors, at Johns Hopkins University, tested blood samples from 22 patients with a form of hereditary colon cancer. Their conversion approach located mutations in all 22, whereas conventional testing verified them only in 10.
This new gene-separation technology is expected to be available this summer through Johns Hopkins, in connection with genetic counseling for people at risk of inherited predisposition for hereditary non-polyposis colorectal cancer and familial adenomatous polyposis.
The authors point out that the technique "should apply to other hereditary cancers, including breast and kidney, as well as a variety of neurological and cardiovascular disease genes."
Upset Delicate Seesaw Between Buildup/ Breakdown Of Bone Fine-Tuned By Amgen
The bones of a human skeleton are not rock-hard, lifeless scaffolding. The body constantly regulates skeletal integrity throughout adult life in higher vertebrates and mammals. Specialized cells inside the bones manage the seemingly contrarian processes of synthesizing and resorbing bone mass. Osteoblastic cells control the buildup; osteoblasts, the whittling down. If osteoclasts overdo their add-on activity, crippling disorders such as osteoporosis and arthritis result. Osteopetrosis, an inherited, systemic disease, can produce even graver consequences.
A key player in this bony interplay is a molecule called RANK (receptor activator of NF-kB).
Cell biologists at Amgen Inc. in Thousand Oaks, Calif., have generated RANK-missing transgenic mice, which lack osteoclasts, and so incur severe osteopetrosis. The researchers reversed the disease by transplanting bone marrow into the knockout animals from mice without this destructive function. Their finding, reported in the Proceedings of the National Academy of Sciences for Feb, 15, 2000, are summed up in the paper's title: "RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism."
The article concludes: "Although the precise events that are required for osteoclastogenesis still remain to be elucidated, the retroviral reconstitution system we have established by using RANK-minus mice should allow unambiguous resolution of the critical mechanism(s) that are downstream of RANK in vivo."