The results, published January 23 in the open-access journal PLoS Pathogens , explain why prior infection by other sexually-transmitted diseases (STDs) makes individuals more susceptible to HIV infection.

The team of researchers, lead by Eric Hunter of Emory University, identified 20 heterosexual couples soon after infection occurred and obtained viral genetic sequences from both partners. They examined the most variable region of the virus' env gene, which encodes a protein forming the outer coat of the virus. Approximately 90% of the couple recipients were found to be infected by a single viral variant of HIV-1. However, that variant was not the same in each case.

For comparison, the researchers also analyzed a group of newly infected individuals who were infected by someone other than their spouse. This group showed more variety in viral sequences, with 3 out of 7 individuals infected by multiple variants. Overall, out of 42 newly infected people studied to date, all five infected by multiple viral variants had evidence of genital inflammation or ulceration.

In these cases, it appears that the bottleneck was enlarged due to the disruption of normally protective mucosal barriers by STDs. These findings suggest that the genital mucosa provides a natural barrier to infection by multiple genetic variants of HIV-1 that can be lowered by inflammatory genital infections.

To identify newly infected individuals, the team collaborated with public health programs directed by Susan Allen of Emory's Rollins School of Public Health that enroll thousands of heterosexual couples with one HIV-positive partner in Rwanda and Zambia.

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Although buffering has a muffling effect on the evolution of a species, it certainly does not hinder it. Jansen: 'I'd say that it's lucky there's buffering. Just imagine if each of the 500,000 differences was immediately expressed in the next generation. From the point of view of the "robustness" of a species, it's necessary that the offspring do not vary too dramatically. But if there's a change in the environment that requires an evolutionary adaptation, then the necessary genetic variation is ready and waiting.'

Hotspots

The discovery means that life scientists should in particular examine the hotspots in the genome when searching for the causes of genetic disorders. In that regard the results of the current research agree with the results of Prof. Cisca Wijmenga of the University Medical Center Groningen, which was published in Nature Reviews Genetics in December. Her research revealed that only a limited number of hotspot genes are involved in the development of numerous immune-related diseases, such as type 1 diabetes, coeliac disease, Crohn's disease and rheumatoid arthritis. Just like Arabidopsis, people differ from each other in millions of positions in their genome, but it's the genotype in the hotspots that is the most relevant. 'When it comes down to it, we are more similar to each other than the major differences in genome sequences suggest.'

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