Biotron adds dengue virus to discovery roster

Canberra biotechnology company Biotron (ASX: BIT) has added dengue virus to the lengthening list of potentially lethal human viruses that possess ion-channel genes.

Biotron researchers, led by Professor Peter Gage of the John Curtin School of Medical Research have now identified ion-channel genes in the Human Immunodeficiency Virus (VPU gene), Severe Acute Respiratory Syndrome virus (Protein E) and dengue fever virus (Protein M). Overseas, researchers have identified ion-channel genes in the influenza virus (M2 gene) and hepatitis C virus(P7).

Biotron's latest discovery means that ion-channel genes have now been found in widely divergent viruses: a retrovirus (HIV), a coronavirus (SARS), a paramyxovirus (influenza), and two distantly related flaviviruses (dengue and hepatitis C).

Biotron CEO Dr Michelle Miller says ion-channel genes may be a common feature of human viruses, hinting at an important role in viral replication.

What that role might be is unclear, says Miller, but Biotron's Virion Project is providing strong evidence for a central role for ion channels role in virus replication.

A proprietary ion-channel blocker designed by Biotron chemists to jam the AIDS virus' VPU ion channel, strongly suppressed the virus' replication in cultured monocyte macrophages. These specialised scavenger cells of the immune-system become reservoirs for HIV replication in the advanced stages of AIDS.

Biotron researchers have now shown that another of the company's patented "plug drugs" blocks replication of the dengue virus.

Cairns has recently experienced a minor epidemic of dengue fever; the mosquito-borne virus is rife in tropical nations, causing an estimated 50 million infections a year. There is no effective treatment.

The symptoms of dengue fever include severe joint and muscle pain; if a victim is subsequently infected by another of the four major strains of the virus, they may develop haemorrhagic dengue, which has a 15 per cent mortality rate.

Miller says virologists were initially sceptical of Gage's idea that ion channels play an key role in virus replication. "But they're now talking about it quite openly, and we're gaining credibility," she said. "Clinicians are also very excited.

"It puts pressure on us to validate our ideas, and to move quickly to develop potential therapeutics and undertake proof-of-concept studies in man."

Although the role of ion-channels in viral replication remains to be determined, Miller says there is some evidence that newly formed virions may exploit them to exit infected host cells, maintaining the infection cycle.

Miller says the attraction of the several classes of "plug drugs" that Biotron is developing is that they are small molecules, and thus potentially less toxic and easier to deliver than other therapies.

With AIDS, the prospect of using a small molecule to lock the retrovirus into macrophages, blocking its replication, was particularly attractive. "Gene therapy is such a hassle," Miller said.