Clonal Sequences Recovered from Plasma from Patients with Residual HIV-1 Viremia and on Intensified Antiretroviral Therapy Are Identical to Replicating Viral RNAs Recovered from Circulating Resting CD4+ T Cells

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2011 Mar 4

PMID 21367910

Citations 63

Authors

Jeffrey A Anderson

Nancie M Archin

William Ince

Daniel Parker

Ann Wiegand

John M Coffin

JoAnn Kuruc

Joseph Eron

Ronald Swanstrom

David M Margolis

Affiliations

Soon will be listed here.

Abstract

Despite successful antiretroviral therapy (ART), low-level viremia (LLV) may be intermittently detected in most HIV-infected patients. Longitudinal blood plasma and resting CD4(+) T cells were obtained from two patients on suppressive ART to investigate the source of LLV. Single-genome sequencing of HIV-1 env from LLV plasma was performed, and the sequences were compared to sequences recovered from limiting-dilution outgrowth assays of resting CD4(+) T cells. The circulating LLV virus clone was identical to virus recovered from outgrowth assays from pools of millions of resting CD4(+) T cells. Understanding the sources of LLV requires evaluation of all possible reservoirs of persistent HIV infection.

Citing Articles

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References

Tamura K, Nei M, Kumar S . Prospects for inferring very large phylogenies by using the neighbor-joining method. Proc Natl Acad Sci U S A. 2004; 101(30):11030-5. PMC: 491989. DOI: 10.1073/pnas.0404206101. View

Kimura M . A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol. 1980; 16(2):111-20. DOI: 10.1007/BF01731581. View

Margolis D, Archin N . Attacking HIV provirus: therapeutic strategies to disrupt persistent infection. Infect Disord Drug Targets. 2006; 6(4):369-76. DOI: 10.2174/187152606779025824. View

Zhang J, Crumpacker C . Hematopoietic stem and progenitor cells in HIV/AIDS and immune reconstitution. Cell Res. 2010; 20(7):745-7. DOI: 10.1038/cr.2010.85. View

Fiebig E, Wright D, Rawal B, Garrett P, Schumacher R, Peddada L . Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS. 2003; 17(13):1871-9. DOI: 10.1097/00002030-200309050-00005. View

Brennan T, Woods J, Sedaghat A, Siliciano J, Siliciano R, Wilke C . Analysis of human immunodeficiency virus type 1 viremia and provirus in resting CD4+ T cells reveals a novel source of residual viremia in patients on antiretroviral therapy. J Virol. 2009; 83(17):8470-81. PMC: 2738142. DOI: 10.1128/JVI.02568-08. View

Archin N, Cheema M, Parker D, Wiegand A, Bosch R, Coffin J . Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection. PLoS One. 2010; 5(2):e9390. PMC: 2826423. DOI: 10.1371/journal.pone.0009390. View

Sahu G, Paar D, Frost S, Smith M, Weaver S, Cloyd M . Low-level plasma HIVs in patients on prolonged suppressive highly active antiretroviral therapy are produced mostly by cells other than CD4 T-cells. J Med Virol. 2008; 81(1):9-15. PMC: 2912142. DOI: 10.1002/jmv.21366. View

Chun T, Davey Jr R, Ostrowski M, Justement J, Engel D, Mullins J . Relationship between pre-existing viral reservoirs and the re-emergence of plasma viremia after discontinuation of highly active anti-retroviral therapy. Nat Med. 2000; 6(7):757-61. DOI: 10.1038/77481. View

10.

Joos B, Fischer M, Kuster H, Pillai S, Wong J, Boni J . HIV rebounds from latently infected cells, rather than from continuing low-level replication. Proc Natl Acad Sci U S A. 2008; 105(43):16725-30. PMC: 2575487. DOI: 10.1073/pnas.0804192105. View

11.

Coiras M, Lopez-Huertas M, Perez-Olmeda M, Alcami J . Understanding HIV-1 latency provides clues for the eradication of long-term reservoirs. Nat Rev Microbiol. 2009; 7(11):798-812. DOI: 10.1038/nrmicro2223. View

12.

Tamura K, Dudley J, Nei M, Kumar S . MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol. 2007; 24(8):1596-9. DOI: 10.1093/molbev/msm092. View

13.

Shankarappa R, Margolick J, Gange S, Rodrigo A, Upchurch D, Farzadegan H . Consistent viral evolutionary changes associated with the progression of human immunodeficiency virus type 1 infection. J Virol. 1999; 73(12):10489-502. PMC: 113104. DOI: 10.1128/JVI.73.12.10489-10502.1999. View

14.

Abrahams M, ANDERSON J, Giorgi E, Seoighe C, Mlisana K, Ping L . Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants. J Virol. 2009; 83(8):3556-67. PMC: 2663249. DOI: 10.1128/JVI.02132-08. View

15.

Montaner L, Crowe S, Aquaro S, Perno C, Stevenson M, Collman R . Advances in macrophage and dendritic cell biology in HIV-1 infection stress key understudied areas in infection, pathogenesis, and analysis of viral reservoirs. J Leukoc Biol. 2006; 80(5):961-4. DOI: 10.1189/jlb.0806488. View

16.

Salazar-Gonzalez J, Bailes E, Pham K, Salazar M, Guffey M, Keele B . Deciphering human immunodeficiency virus type 1 transmission and early envelope diversification by single-genome amplification and sequencing. J Virol. 2008; 82(8):3952-70. PMC: 2293010. DOI: 10.1128/JVI.02660-07. View

17.

Bailey J, Sedaghat A, Kieffer T, Brennan T, Lee P, Wind-Rotolo M . Residual human immunodeficiency virus type 1 viremia in some patients on antiretroviral therapy is dominated by a small number of invariant clones rarely found in circulating CD4+ T cells. J Virol. 2006; 80(13):6441-57. PMC: 1488985. DOI: 10.1128/JVI.00591-06. View

18.

Saitou N, Nei M . The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987; 4(4):406-25. DOI: 10.1093/oxfordjournals.molbev.a040454. View

19.

Palmer S, Wiegand A, Maldarelli F, Bazmi H, Mican J, Polis M . New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol. 2003; 41(10):4531-6. PMC: 254331. DOI: 10.1128/JCM.41.10.4531-4536.2003. View

20.

Dornadula G, Zhang H, VanUitert B, Stern J, Livornese Jr L, Ingerman M . Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. JAMA. 1999; 282(17):1627-32. DOI: 10.1001/jama.282.17.1627. View