title: Evolutionary indicators of human immunodeficiency virus type 1 reservoirs and compartments.
abstract: 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.
authors.affiliation: Departmentof Microbiology, University of Washington School of Medicine, Seattle 98195, USA. dnickle@u.washington.edu
authors.forename: David C
authors.initials: DC
authors.lastname: Nickle
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jensen
authors.forename: Daniel
authors.initials: D
authors.lastname: Shriner
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Brodie
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Frenkel
authors.forename: John E
authors.initials: JE
authors.lastname: Mittler
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
mesh_terms: D000465:Algorithms; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes; D004279:DNA, Viral / Q000032:analysis / Q000097:blood; D004197:Disease Reservoirs; D019143:Evolution, Molecular; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D010802:Phylogeny; D011237:Predictive Value of Tests; D017422:Sequence Analysis, DNA; D019562:Viral Load; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D004279:DNA, Viral