26 May 2003 12:00 GMT

by Laura Spinney

An invading virus responds to a malnourished host by mutating faster and stepping up its virulence, according to unpublished US research. The findings could point to a powerful mechanism behind the increased susceptibility of underfed humans to viral infection.

Melinda Beck of the Department of Pediatrics at the University of North Carolina at Chapel Hill had already shown that dietary deficiency in mice can bring about an increase in viral virulence that persists even when the virus is transmitted to adequately fed animals. In other words, she told delegates attending the annual meeting of the American Society for Microbiology (ASM), she had strong evidence that malnutrition affects not only the host but also the genome of the virus.

The next step was to see if the same held true for humans. In unpublished research, Beck has set out to investigate a series of epidemics of infectious neurological disease that took place in Cuba in the 1990s. The Cuban economy, already shaky, took a further dive in 1989 when Russia withdrew its aid. From that year on, vitamin deficiencies became a widespread problem in the country.

Beck noted that the years 1990-1991 saw an outbreak of meningitis, which was followed in 1993 by an epidemic of optic and peripheral neuropathy that affected 50,000 people, most of whom were young men. In 1994, the authorities began to distribute B vitamin supplements, and in 2000, there was yet another epidemic of meningitis.

She took samples of the viral strains that contributed to all three epidemics, sequenced their genomes and built up a phylogenetic tree to show the evolutionary distance between them - both in terms of their DNA sequences and the amino acids they contained.

The trees showed that the strains responsible for the 2000 meningitis and the 1993 neuropathy epidemics clustered together, and in evolutionary terms were distant from the cluster of strains that caused the first meningitis outbreak.

But intriguingly, one of the eight strains that contributed to that earlier meningitis outbreak fell neatly between the two main groupings. Of the 23 amino acids that differed between the two, this outlying strain possessed roughly half of those present in the earlier cluster, and half of those present in the later one.

That, says Beck, is highly indicative of some kind of transition in viral virulence that began with the onset of malnutrition.

She also points out that the evolutionary proximity of the neuropathy and later meningitis strains suggests that nutritional supplements helped reverse the dietary deficiencies and slow down the rate of viral mutation, which explains why so little genomic change took place in the seven years separating the two epidemics.

By contrast, a huge amount of mutation separated the 1990-1991 and 1993 epidemics - the period of the worst malnutrition - but only two years in real time.

"Nutritional deficiencies drive viral changes over a very short timeframe," concludes Beck.

Kevin Fritsche of the University of Missouri in Columbia says the findings are very exciting. "We now need to think of improving nutrition in developing countries not only for their own sake, but also in terms of controlling infectious diseases on a global scale," he says.

Malnutrition is currently estimated to be responsible for 55% of global mortality.