ANN ARBOR—” Outbreak,” the current hit movie about a monkey that infects residents of a California town with a newly-evolved lethal virus, has many similarities to the way most scientists believe HIV, the virus that causes AIDS, originated in primates and spread to humans. It makes a great story but, when it comes to HIV, the evidence shows that human beings are just as likely to have infected the monkey, says University of Michigan evolutionary biologist David Mindell.

” The conventional wisdom is that HIV is a new virus transmitted to humans from African monkeys, chimpanzees or other primates within the last 50 years,” said Mindell, U- M assistant professor of biology. ” However, a careful analysis of the evolutionary relationships among HIV-related viruses does not support this popular view. Based on the current evidence, it’s equally possible that HIV is a very old virus, which may have co-existed with people in isolated parts of Africa or elsewhere for hundreds or thousands of years. ”

Mindell emphasized he is not claiming that humans are the ancestral host species for HIV. Rather, his point is that there is not enough evidence to resolve the issue either way.

With colleagues Jeffrey W. Shultz of the University of Maryland and Paul W. Ewald of Amherst College, Mindell published a report summarizing this point of view in the current issue of Systematic Biology.

According to Mindell, many scientists have assumed that virulent viruses are new and non-virulent viruses are old. Like all parasites, viruses need a living host in order to survive and reproduce. So it is logical to assume that, over time, evolution tends to produce a ” state of peaceful coexistence” between the host and parasite.

But it does not always work that way, cautioned Mindell.

“Just as a virus can change its effects from pathogenic to benign, it can change from benign to pathogenic. All it takes is some change in the environment, including a change in the host’s behavior, to give virulent viruses a reproductive advantage. ”

In the study, Mindell and his co-authors compared DNA patterns in genes from 28 viral isolates obtained from the Los Alamos HIV sequence database and GenBank. Samples included viruses found in humans (HIV1 and HIV2), the simian strains of the virus found in wild non-human primates (SIV) and the feline form found in cats (FIV). Mindell selected and compared specific genes from all the viruses, looking for matching patterns of DNA. ” Viruses with the most shared DNA sequence characters are most likely to have shared a recent common ancestor,” Mindell explained.

Mindell conducted studies of the evolutionary rates of change for different genes and different kinds of DNA substitutions. This information was then used in phylogenetic analyses of the genes, which produced a ” tree” – relationships between organisms. The tree clusters organisms into groups called clades having many genetic characteristics in common. Mindell defines a clade as ” all and only the descendants from a single common ancestor. ” After creating the tree, Mindell looked for the simplest possible sequence of cross-species jumps by the virus, based on the fact that host-species shifts tend to be rare events.

” The tree shows humans to be the ancestral host species for two of the clades, which include viruses from non- humans,” Mindell said. ” The original ancestral host for the entire HIV/SIV family of viruses could be either human or non-human primates. To resolve the question, we need more viral samples from non-human primates. ”

Mindell also believes that failure to find HIV in human blood samples collected in seven African locations during the 1960s and 1970s does not prove that HIV is a new virus in humans. ” Vast regions of Africa and millions of people were not included in this survey,” he said. ” HIV could easily have been present in several small, isolated human populations, which were not sampled. ”

If HIV is an old virus, it originally must have been much less deadly than it is today. Mindell believes recent changes in the sexual behavior of its human host could have encouraged the spread of a more virulent strain of the sexually-transmitted virus.

In isolated, traditional populations where numerous sexual partners were uncommon, a virus that reproduced slowly and allowed its human host to live for many years would have had the best chance of evolutionary survival, because it gives the virus the longest possible time to infect a second human host, Mindell explained.

In some modern populations where individuals have many more sexual partners, a virus that reproduces rapidly has a better chance of infecting as many new hosts as possible — even if it quickly kills off the first host in the process.

” It suggests that changing human behavior may have been a key factor responsible for the evolution of HIV virulence and the development of the AIDS epidemic,” Mindell said.

The research was supported by the National Science Foundation and the Alfred P. Sloan Foundation.

Systematic BiologyAlfred P. Sloan Foundation