By David N. Leff
Editor¿s note: Science Scan is a roundup of recently published biotechnology-relevant research.
On the maxim of setting a thief to catch a thief, a hepatitis virus has latched on to the AIDS virus, and attenuated its lethal progress.
The do-gooder microorganism is hepatitis G (HGV) ¿ also referred to as GB virus C ¿ THE latest addition to the alphabet soup of hepatitis viruses from A to E. Reports of two large-scale, long-term prospective trials of HGV¿s beneficial influence on HIV infection run in the current New England Journal of Medicine (NEJM), dated Sept. 6, 2001. The first paper, which leads the journal¿s contents, is titled: ¿Effect of coinfection with GB virus C on survival among patients with HIV infection.¿ Its authors are at the University of Iowa College of Medicine and the Veterans Affairs Medical Center, both in Iowa City.
Immediately following in the NEJM is a parallel second article: ¿Infection with GB virus C and reduced mortality among HIV-infected patients.¿ Its co-authors are gastroenterologists, hepatologists and immunologists at the Medizinische Hochschule in Hannover, Germany.
Both groups concluded that HGV infection is common in HIV-infected people, and is associated with significantly improved survival. Thus, of 362 HIV-infected Iowa patients, 144 (39.8 percent) had HGV in their blood. Of these, only 41 (28.5 percent) died during the four-year follow-up period, whereas 123 (56.4 percent) of the 218 non-HGV patients succumbed to the AIDS virus.
Hepatitis G virus was first identified in 1995 in a preserved blood sample archived 40 years ago from a surgeon diagnosed with non-A-E hepatitis. Scientists at Genelabs Technologies Inc. in Redwood City, Calif., rediscovered the hep G virus in the mid-1990s. In collaboration with the Centers for Disease Control and the NIH, the company identified HGV in a patient, and sequenced its entire genome.
It¿s a positive-sense, single-stranded RNA virus of approximately 9,400 nucleotides, belonging to the Flaviviridae viral family, which is distantly related to the human viruses of hepatitis C, yellow fever and dengue. Despite this sinister family tree, hepatitis G itself has never been found to cause disease in any human being. But it¿s prevalent worldwide, and is a frequent fellow traveler in people infected with HIV or hepatitis C.
However, the Iowa paper reports finding 1.8 percent of HGV infection in healthy, volunteer blood donors; 15 percent in hep C-positive persons; and up to 35 percent in HIV-positive individuals. They tested 362 HIV-infected patients treated in their HIV clinic between 1998 and 2000. The 41 percent of HGV infection among patients who had acquired HIV by sexual transmission was similar to the 35.6 percent who got it by needle exchange.
Besides in vivo human data, the Iowa team studied in vitro behavior of the piggy-backing hepatitis G virus on HIV. ¿The inhibitory effect of [HGV] replication on HIV growth in cell culture,¿ they report, ¿was evident when HIV infection preceded [HGV] infection . . . . The mechanics of inhibition therefore appears to operate during a stage of HIV replication after attachment and entry.¿
The German paper, besides detailing comparable survival results, added: ¿The introduction of highly active antiretroviral therapy [HAART] in 1996 has improved the prognosis of HIV-infected patients dramatically. . . . but the patients coinfected with [HGV] still have a significantly better survival rate [than] patients negative for [HGV] RNA.¿
The Iowa article concludes: ¿The possible role of [HGV] infection as a treatment for HIV infection remains to be evaluated.¿ But an accompanying editorial by scientists at Northwestern University, Chicago, warns: ¿Any suggestion that the intentional infection of persons with [HGV] be explored as a therapeutic approach for HIV infection is premature. Moreover, given that [HGV] frequently coexists with other pathogens, intentional infection . . . is inadvisable and inherently dangerous.¿
Vibes Of Quivering Mice Lead To Nerve Loss Resembling Charcot-Marie-Tooth Syndrome
Despite its name, Charcot-Marie-Tooth disease (CMTD) is not a dental affliction. Its third moniker is an eponym for British neurologist Howard Henry Tooth, who described CMTD in the late 19th century. By coincidence, so did two French neurologists, Jean-Martin Charcot and Pierre Marie.
Today the polyneuropathy CMT syndrome (a.k.a. peroneal muscular atrophy) is the most common inherited neuropathy, with a prevalence of at least one in 2,500 in the U.S. population. It shares with multiple sclerosis, muscular dystrophy and amyotrophic lateral sclerosis a critical defect in the body¿s peripheral nerves ¿ deterioration and destruction of the myelin that sheaths nerve axons. But unlike these better-known neuropathies, CMTD is not life threatening.
It¿s first noticed in late childhood or early adult years for its abnormally high arches, which causes walking on tiptoes. As the syndrome progresses, foot and leg muscles weaken and waste, as do hands and arms, while ankles sprain readily. It¿s all due to demyelination of the peripheral nerves involved.
Mice are long-favored laboratory models of dysmyelination disorders. These animals share some peculiar bodily vibes. Some are tremblers, others shivererers, still others quiverers. Trembler mice simulate the demyelination occurring in multiple sclerosis patients. The so-called ¿quivering¿ mouse ¿ featuring progressive ataxia, hind-limb paralysis, deafness and tremor ¿ arose spontaneously in 1953. The gene mutation responsible for its complex disorder remained a puzzle until now.
This veil has at last been drawn in a paper published online Aug. 20, 2001, in Nature Genetics titled: ¿Mutant b-spectrin 4 causes auditory and motor neuropathies in quivering mice.¿ Its authors are at the University of Washington in Seattle. They developed a detailed genetic map of the region on mouse chromosome 7, which they suspected of harboring the quivering gene. One gene they fingered, beta-spectrin 4, is expressed in the nerves that control muscle movement.
¿Humans with mutations in beta-spectrin 4,¿ the paper concludes, ¿might show symptoms ranging from non-syndromic auditory neuropathy to syndromic peripheral motor neuropathies such as Charcot-Marie-Tooth syndrome, one form of which maps to human chromosome 19¿s long arm in the region homologous to quivering.¿