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Journal of Virology, November 2003, p. 12122-12131, Vol. 77, No. 22
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.22.12122-12131.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Subpopulations of Equine Infectious Anemia Virus Rev Coexist In Vivo and Differ in Phenotype

Prasith Baccam,^1,2, Robert J. Thompson,² Yuxing Li,² Wendy O. Sparks,² Michael Belshan,² Karin S. Dorman,^3,4 Yvonne Wannemuehler,² J. Lindsay Oaks,⁵ James L. Cornette,¹ and Susan Carpenter^2*

Departments of Mathematics,¹ Veterinary Microbiology and Preventive Medicine,² Statistics,³ Genetics, Development and Cell Biology, Iowa State University, Ames, Iowa,⁴ Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington⁵

Received 29 April 2003/ Accepted 11 August 2003

Lentiviruses exist in vivo as a population of related, nonidentical genotypes, commonly referred to as quasispecies. The quasispecies structure is characteristic of complex adaptive systems and contributes to the high rate of evolution in lentiviruses that confounds efforts to develop effective vaccines and antiviral therapies. Here, we describe analyses of genetic data from longitudinal studies of genetic variation in a lentivirus regulatory protein, Rev, over the course of disease in ponies experimentally infected with equine infectious anemia virus. As observed with other lentivirus data, the Rev variants exhibited a quasispecies character. Phylogenetic and partition analyses suggested that the Rev quasispecies comprised two distinct subpopulations that coexisted during infection. One subpopulation appeared to accumulate changes in a linear, time-dependent manner, while the other evolved radially from a common variant. Over time, the two subpopulations cycled in predominance coincident with changes in the disease state, suggesting that the two groups differed in selective advantage. Transient expression assays indicated the two populations differed significantly in Rev nuclear export activity. Chimeric proviral clones containing Rev genotypes representative of each population differed in rate and overall level of virus replication in vitro. The coexistence of genetically distinct viral subpopulations that differ in phenotype provides great adaptability to environmental changes within the infected host. A quasispecies model with multiple subpopulations may provide additional insight into the nature of lentivirus reservoirs and the evolution of antigenic and drug-resistant variants.

Present address: Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545.

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