AIDSWEEKLY Plus; Monday, May 31, 2004
Staff Medical Writers

"Genetic recombination is believed to assist HIV-1 diversification and escape from host immunity and antiviral therapies, yet this process remains largely unexamined within the natural target-cell populations," wrote scientists in the Proceedings of the National Academy of Sciences USA.

A method was developed "for measuring HIV-1 recombination directly that employs reporter viruses bearing functional enhanced yellow fluorescent protein (YFP) and enhanced cyan fluorescent protein (CFP) genes in which recombination produces a modified GFP gene and GFP fluorescence in the infected cells. These reporter viruses allow simultaneous quantification of the dynamics of HIV-1 infection, coinfection, and recombination in cell culture and in animal models by flow-cytometric analysis," D.N. Levy and colleagues reported.

"Multi-round infection assays revealed that productive cellular coinfection was subject to little functional inhibition. As a result, generation of recombinants proceeded according to the square of the infection rate during HIV-1 replication in T lymphocytes and within human thymic grafts in severe combined immunodeficient (SCID)-hu (Thy/Liv) mice," said Levy and coworkers.

"These results suggest that increases in viral load may confer a compounding risk of virus escape by means of recombinational diversification. A single round of replication in T lymphocytes in culture generated an average of nine recombination events per virus, and infection of macrophages led to approximately 30 crossover events, making HIV-1 up to an order of magnitude more recombinogenic than recognized previously and demonstrating that the infected cell exerts a profound influence on the frequency of recombination," concluded investigators.

Levy and colleagues published their study in Proceedings of the National Academy of Sciences USA (Dynamics of HIV-1 recombination in its natural target cells. Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4204-9.

For more information, contact D.N. Levy, Department of Medicine, University of Alabama at Birmingham, 848 Kaul Building, 720 20th Street South, Birmingham, AL 35294-0024, USA.

Publisher contact information for the journal Proceedings of the National Academy of Sciences USA is: National Academy Sciences, 2101 Constitution Avenue NW, Washington, DC 20418, USA.

The information in this article comes under the major subject areas of AIDS and HIV, Recombination and Genomics.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Levy DN, Aldrovandi GM, Kutsch O, et al., "Dynamics of HIV-1 recombination in its natural target cells", Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4204-9

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