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Journal of Virology, May 2003, p. 5540-5546, Vol. 77, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.9.5540-5546.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Evolutionary Indicators of Human Immunodeficiency Virus Type 1 Reservoirs and Compartments

David C. Nickle,1* Mark A. Jensen,1 Daniel Shriner,1 Scott J. Brodie,2 Lisa M. Frenkel,2,3 John E. Mittler,1 and James I. Mullins1,2

Departments of Microbiology,1 Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington 98195,2 Children's Hospital and Medical Center, Seattle, Washington 981053

Received 29 April 2002/ Accepted 30 January 2003

In vivo virologic compartments are cell types or tissues between which there is a restriction of virus flow, while virologic reservoirs are cell types or tissues in which there is a relative restriction of replication. The distinction between reservoirs and compartments is important because therapies that would be effective against a reservoir may not be effective against viruses produced by a given compartment, and vice versa. For example, the use of cytokines to "flush out" long-lived infected cells in patients on highly active antiretroviral therapy (T. W. Chun, D. Engel, M. M. Berrey, T. Shea, L. Corey, and A. S. Fauci, Proc. Natl. Acad. Sci. USA 95:8869-8873, 1998) may be successful for a latent reservoir but may not impact a compartment in which virus continues to replicate because of poor drug penetration. Here, we suggest phylogenetic criteria to illustrate, define, and differentiate between reservoirs and compartments. We then apply these criteria to the analysis of simulated and actual human immunodeficiency virus type 1 sequence data sets. We report that existing statistical methods work quite well at detecting viral compartments, and we learn from simulations that viral divergence from a calculated most recent common ancestor is a strong predictor of viral reservoirs.

* Corresponding author. Mailing address: Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195-8070. Phone: (206) 732-6150. Fax: (206) 732-6167. E-mail: dnickle{at}u.washington.edu.

Journal of Virology, May 2003, p. 5540-5546, Vol. 77, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.9.5540-5546.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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