This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kieffer, T. L.
Right arrow Articles by Siliciano, R. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kieffer, T. L.
Right arrow Articles by Siliciano, R. F.

 Previous Article  |  Next Article 

Journal of Virology, February 2005, p. 1975-1980, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1975-1980.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

G->A Hypermutation in Protease and Reverse Transcriptase Regions of Human Immunodeficiency Virus Type 1 Residing in Resting CD4+ T Cells In Vivo

Tara L. Kieffer,1 Patty Kwon,1 Richard E. Nettles,1 Yefei Han,1 Stuart C. Ray,1 and Robert F. Siliciano1,2*

Department of Medicine, Johns Hopkins University School of Medicine,1 Howard Hughes Medical Institute, Baltimore, Maryland2

Received 10 August 2004/ Accepted 9 September 2004


arrow
ABSTRACT
 
In vitro studies have shown that the host cytidine deaminase APOBEC3G causes lethal hypermutation in human immunodeficiency virus type 1 reverse transcripts unless its incorporation into virions is blocked by Vif. By examining stably archived sequences in resting CD4+ T cells, we show that hypermutation occurs in most if not all infected individuals. Hypermutated sequences comprised >9% of archived species in resting CD4+ T cells but were not found in plasma virus. Mutations occurred in predicted contexts, with notable hotspots. Thus, defects in Vif function in vivo give rise to hypermutated viral genomes that can be integrated but do not produce progeny viruses.


arrow
TEXT
 
A component of innate immune defense against viruses is ABOBEC3G, a cytidine deaminase which causes G->A hypermutation in retroviral genomes (9, 11, 16, 18, 26, 35, 36). ABOBEC3G is incorporated into assembling virions and then deaminates cytidines of the single-stranded viral cDNA that is initially synthesized by reverse transcriptase (RT) upon entry of the virus into a new host cell (11, 16, 18, 35, 36). This C->U deamination on the minus strand of the reverse transcript leads to fixation of G->A mutations. Pioneering work by Sheehy et al. identified APOBEC3G as an antiviral factor and showed that human immunodeficiency virus type 1 (HIV-1) Vif overcomes its effects (26). Vif counteracts APOBEC3G by inhibiting its translation and accelerating its degradation, thereby preventing APOBEC3G incorporation into HIV-1 virions (19, 20, 25, 27, 30). Studies of target sequence specificity of ABOBEC3G have revealed a context dependence for the two nucleotides immediately upstream of the targeted dC (1, 11, 35), consistent with reports of G->A hypermutation in HIV-1 sequences from infected individuals (3, 8, 13). In these studies, minus-strand C->U deamination resulted in fixation of G->A mutations within GA and GG dinucleotides with an extreme bias for GGG sequences (3, 13, 31). Within hypermutated sequences, 20 to 94% of guanine nucleotides in these contexts were mutated (13). Recent studies have delineated the preferences of ABOBEC3G and ABOBEC3F, a closely related protein of similar function (33, 34), as GG and GA, respectively (17, 33).

Most studies of the antiviral effects of APOBEC3G have utilized Vif– HIV-1 constructs, and there remains uncertainty about how often G->A hypermutation occurs in HIV-1-infected individuals and about the fate of hypermutated viruses. Janini et al. found hypermutation in 43% of patient samples (13). Hypermutated sequences had in-frame stop codons that would interfere with the production of viral proteins (13). However, the replication defect shown by Vif– viruses may actually operate at an early, postentry stage in viral replication and decrease the formation of proviruses (29, 32). One possibility is that the deoxyuridines produced by deamination undergo uracil excision by uracil-DNA glycosylases, exposing the viral cDNA to nucleases (11).

To understand the nature and distribution of hypermutated sequences in vivo, we analyzed the protease and RT regions of HIV-1 sequences obtained from resting CD4+ T cells of nine patients who had prolonged suppression of viremia to below the limit of detection on highly active antiretroviral therapy (HAART). In patients on successful long-term HAART, labile unintegrated forms of HIV-1 decay (2, 22), and resting CD4+ T cells harbor stably integrated, latent viral genomes, some of which are replication competent (4, 5, 10). This cellular reservoir persists in patients on HAART (6, 21, 28) and continually releases virus into the plasma at low levels (12, 14). We analyzed hypermutation in both the cellular and plasma compartments of these patients.

Resting CD4+ T cells were isolated from peripheral blood mononuclear cells by use of negative selection to remove monocytes, natural killer (NK) cells, B cells, CD8+ T cells, and activated CD4+ T cells as previously described (7). The resulting populations were >90% pure. pol gene sequences from resting cells were obtained by a single genome sequencing method (P. Kwon, M. Wind-Rotolo, and R. F. Siliciano, unpublished data). Plasma sequences were obtained by frequent sampling over a 3-month period and an ultrasensitive RT-PCR capable of separately genotyping RT and protease from patients with viral loads below 50 copies/ml (14). Sequences were analyzed using a program (www.hiv.lanl.gov/HYPERMUT/hypermut.html) that compares each patient sequence to a patient-specific consensus to determine the frequency and context of G->A mutations (23). Hypermutated sequences were defined as having >5% of the total Gs mutated to A but <1% A->G mutations.

Of 2,024 independent RT and protease sequences from the plasma virus of nine patients, not a single one was hypermutated. In contrast, from a total of 317 independent pol clones from the latent cellular reservoir, hypermutation was detected in 19 of 302 (6.3%) protease sequences and 21 of 309 (6.8%) RT sequences. Both protease and RT were hypermutated in 12 clones. Thus, there were a minimum of 28 (8.8%) hypermutated genomes among the 317 pol clones. This is a minimal estimate, because sequencing repeatedly failed for some pol clones (15 protease and 8 RT sequences), possibly due to hypermutation, and because sequencing additional regions of the viral genome, particularly env and the 5' half of nef (35), may have revealed additional hypermutation. At least one hypermutated sequence was found with each patient studied. Phylogenetic analysis showed patient-specific clustering and extreme divergence of the hypermutated sequences within patient-specific clusters (Fig. 1). The routine detection of hypermutated sequences in resting CD4+ T cells of patients with prolonged suppression of active viral replication on HAART suggests that hypermutated viral genomes can enter the stable pool of integrated HIV-1 DNA in these cells. The absence of hypermutated plasma sequences indicates that hypermutation blocks virus production from these proviruses.



View larger version (16K):
[in this window]
[in a new window]
  		FIG. 1. Representative phylogenetic tree of RT sequences from patient 136. Independent sequences obtained from resting CD4+ T cells (•) and from plasma ({triangleup}) of patient 136 are displayed along with the consensus sequences from the other patients and the reference sequence HXB2 (15). Independent isolates with identical sequences are represented by one symbol, with the number of isolates indicated next to the symbol. A hypermutated sequence (136.G2) with 21 G->A mutations is enclosed in a square. The reference sequence HXB2 was used as an outgroup. Neighbor-joining phylogenetic analysis of RT positions 2640 to 3233 (relative to HXB2) was carried out as previously described (24).

Within hypermutated sequences, G->A mutations were found at an average of 11% (RT) and 13.5% (protease) of all Gs (range, 5 to 22%), while only 0.18% (RT) and 0.44% (protease) of As were mutated to guanine (Table 1). In 98% of the cases, mutations were found in either GA or GG dinucleotides, with about 20% in GA and 80% in either GG or GGG sequences. In contrast, Janini et al. (13) noted a 3F-like preference for mutation within the GA context in protease sequences from unfractionated peripheral blood mononuclear cells of viremic patients. We found a preference for hypermutation at Gs preceded by T, consistent with a recent study defining TGGG as the tetranucleotide consensus sequence for ABOBEC3G (35). Our results are consistent with the idea of both ABOBEC3G and ABOBEC3F contributing to in vivo hypermutation.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Analysis of frequency and sequence context of G -> A mutations

Mutational hotspots, defined as G->A mutations in >50% of hypermutated sequences, were identified in the protease and RT genes (Table 2 and Table 3). The substitution at nucleotide (nt) 125 in protease was found in 63% of sequences and resulted in a stop codon. Four other hotspots resulted in a change at a glycine residue. This is as expected, since glycine codons (GGN) contain the targeted GG dinucleotide. In RT, nine hotspots were identified (Table 3). The Gs at nt 151, 263, 333, and 690 occurred at the beginning of GGG trinucleotides and were mutated in 80 to 95% of sequences. RT mutations resulted in substitutions at methionine (n = 4), tryptophan (n = 2), or glycine (n = 2). The mutations in methionine codons (ATG) produced changes to isoleucine (ATA), one of which was at amino acid 184 and corresponded to a known intermediate in the pathway to lamivudine resistance. The mutations within tryptophan codons resulted in stop codons at amino acids 88 and 212. The mutation at nt 333 produced a synonymous change detected in 95% of the sequences.


View this table:
[in this window]
[in a new window]
  		TABLE 2. Detailed analysis of G -> A mutations in the protease gene of 19 hypermutated sequences from the resting CD4+ T cells of eight patients on HAART


View this table:
[in this window]
[in a new window]
  		TABLE 3. Detailed analysis of G -> A mutations in the RT gene of 21 hypermutated sequences from the resting CD4+ T cells of nine patients on HAART

We have detected hypermutated sequences in resting CD4+ T cells from patients who had prolonged suppression of viremia on HAART. Hypermutated sequences with characteristic APOBEC3G/F-mediated changes constituted >9% of the viral genomes in this compartment and were found in every patient. This level may reflect some degree of accumulation of defective genomes that do not direct the synthesis of a full complement of viral proteins, thereby sparing the infected cell from viral cytopathic effects. Our data suggest that mutated viral genomes are able to integrate into cellular DNA and persist in resting CD4+ T cells even when viral replication is halted with HAART. However, these hypermutated genomes are subsequently incapable of producing virus, as indicated by the fact that the viruses released into the plasma at low level in patients on HAART were completely devoid of hypermutated sequences.


arrow
ACKNOWLEDGMENTS
 
This work was supported by the Johns Hopkins University School of Medicine General Clinical Research Center, grant number M01-RR00052, from the National Center for Research Resource/National Institutes of Health and by National Institutes of Health grants AI43222 and AI51178 and a grant from the Doris Duke Charitable Foundation.


arrow
FOOTNOTES
 
* Corresponding author. Mailing address: Department of Medicine, Johns Hopkins University School of Medicine, 879 Broadway Research Bldg., 733 N. Broadway, Baltimore, MD 21205. Phone: (410) 955-2958. Fax: (443) 287-6218. E-mail: rsiliciano{at}jhmi.edu. Back


arrow
REFERENCES
 
    1
  1. Beale, R. C., S. K. Petersen-Mahrt, I. N. Watt, R. S. Harris, C. Rada, and M. S. Neuberger. 2004. Comparison of the differential context-dependence of DNA deamination by APOBEC enzymes: correlation with mutation spectra in vivo. J. Mol. Biol. 337:585-596.[CrossRef][Medline]
    2. 2
  2. Blankson, J. N., D. Persaud, and R. F. Siliciano. 2002. The challenge of viral reservoirs in HIV-1 infection. Annu. Rev. Med. 53:557-593.[CrossRef][Medline]
    3. 3
  3. Borman, A. M., C. Quillent, P. Charneau, K. M. Kean, and F. Clavel. 1995. A highly defective HIV-1 group O provirus: evidence for the role of local sequence determinants in G->A hypermutation during negative-strand viral DNA synthesis. Virology 208:601-609.[CrossRef][Medline]
    4. 4
  4. Chun, T. W., L. Carruth, D. Finzi, X. Shen, J. A. DiGiuseppe, H. Taylor, M. Hermankova, K. Chadwick, J. Margolick, T. C. Quinn, Y. H. Kuo, R. Brookmeyer, M. A. Zeiger, P. Barditch-Crovo, and R. F. Siliciano. 1997. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387:183-188.[CrossRef][Medline]
    5. 5
  5. Chun, T. W., D. Finzi, J. Margolick, K. Chadwick, D. Schwartz, and R. F. Siliciano. 1995. In vivo fate of HIV-1-infected T cells: quantitative analysis of the transition to stable latency. Nat. Med. 1:1284-1290.[CrossRef][Medline]
    6. 6
  6. Finzi, D., J. Blankson, J. D. Siliciano, J. B. Margolick, K. Chadwick, T. Pierson, K. Smith, J. Lisziewicz, F. Lori, C. Flexner, T. C. Quinn, R. E. Chaisson, E. Rosenberg, B. Walker, S. Gange, J. Gallant, and R. F. Siliciano. 1999. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat. Med. 5:512-517.[CrossRef][Medline]
    7. 7
  7. Finzi, D., M. Hermankova, T. Pierson, L. M. Carruth, C. Buck, R. E. Chaisson, T. C. Quinn, K. Chadwick, J. Margolick, R. Brookmeyer, J. Gallant, M. Markowitz, D. D. Ho, D. D. Richman, and R. F. Siliciano. 1997. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278:1295-1300.[Abstract/Free Full Text]
    8. 8
  8. Fitzgibbon, J. E., S. Mazar, and D. T. Dubin. 1993. A new type of G->A hypermutation affecting human immunodeficiency virus. AIDS Res. Hum. Retrovir. 9:833-838.[Medline]
    9. 9
  9. Goff, S. P. 2003. Death by deamination: a novel host restriction system for HIV-1. Cell 114:281-283.[CrossRef][Medline]
    10. 10
  10. Han, Y., K. Lassen, D. Monie, A. R. Sedaghat, S. Shimoji, X. Liu, T. C. Pierson, J. B. Margolick, R. F. Siliciano, and J. D. Siliciano. 2004. Resting CD4+ T cells from human immunodeficiency virus type 1 (HIV-1)-infected individuals carry integrated HIV-1 genomes within actively transcribed host genes. J. Virol. 78:6122-6133.[Abstract/Free Full Text]
    11. 11
  11. Harris, R. S., K. N. Bishop, A. M. Sheehy, H. M. Craig, S. K. Petersen-Mahrt, I. N. Watt, M. S. Neuberger, and M. H. Malim. 2003. DNA deamination mediates innate immunity to retroviral infection. Cell 113:803-809.[CrossRef][Medline]
    12. 12
  12. Hermankova, M., S. C. Ray, C. Ruff, M. Powell-Davis, R. Ingersoll, R. T. D'Aquila, T. C. Quinn, J. D. Siliciano, R. F. Siliciano, and D. Persaud. 2001. HIV-1 drug resistance profiles in children and adults with viral load of <50 copies/ml receiving combination therapy. JAMA 286:196-207.[Abstract/Free Full Text]
    13. 13
  13. Janini, M., M. Rogers, D. R. Birx, and F. E. McCutchan. 2001. Human immunodeficiency virus type 1 DNA sequences genetically damaged by hypermutation are often abundant in patient peripheral blood mononuclear cells and may be generated during near-simultaneous infection and activation of CD4+ T cells. J. Virol. 75:7973-7986.[Abstract/Free Full Text]
    14. 14
  14. Kieffer, T. L., M. M. Finucane, R. E. Nettles, T. C. Quinn, K. W. Broman, S. C. Ray, D. Persaud, and R. F. Siliciano. 2004. Genotypic analysis of HIV-1 drug resistance at the limit of detection: virus production without evolution in treated adults with undetectable HIV loads. J. Infect. Dis. 189:1452-1465.[CrossRef][Medline]
    15. 15
  15. Kuiken, C., B. Foley, B. Hahn, P. Marx, F. McCutchan, J. Mellors, S. Wolinsky, and B. Korber. 2001. HIV sequence compendium 2001. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, N.M.
    16. 16
  16. Lecossier, D., F. Bouchonnet, F. Clavel, and A. J. Hance. 2003. Hypermutation of HIV-1 DNA in the absence of the Vif protein. Science 300:1112.[Free Full Text]
    17. 17
  17. Liddament, M. T., W. L. Brown, A. J. Schumacher, and R. S. Harris. 2004. APOBEC3F properties and hypermutation preferences indicate activity against HIV-1 in vivo. Curr. Biol. 14:1385-1391.[CrossRef][Medline]
    18. 18
  18. Mangeat, B., P. Turelli, G. Caron, M. Friedli, L. Perrin, and D. Trono. 2003. Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature 424:99-103.[CrossRef][Medline]
    19. 19
  19. Mariani, R., D. Chen, B. Schrofelbauer, F. Navarro, R. Konig, B. Bollman, C. Munk, H. Nymark-McMahon, and N. R. Landau. 2003. Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell 114:21-31.[CrossRef][Medline]
    20. 20
  20. Marin, M., K. M. Rose, S. L. Kozak, and D. Kabat. 2003. HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nat. Med. 9:1398-1403.[CrossRef][Medline]
    21. 21
  21. Persaud, D., T. Pierson, C. Ruff, D. Finzi, K. R. Chadwick, J. B. Margolick, A. Ruff, N. Hutton, S. Ray, and R. F. Siliciano. 2000. A stable latent reservoir for HIV-1 in resting CD4+ T lymphocytes in infected children. J. Clin. Investig. 105:995-1003.[Medline]
    22. 22
  22. Pierson, T. C., Y. Zhou, T. L. Kieffer, C. T. Ruff, C. Buck, and R. F. Siliciano. 2002. Molecular characterization of preintegration latency in human immunodeficiency virus type 1 infection. J. Virol. 76:8518-8531.[Abstract/Free Full Text]
    23. 23
  23. Rose, P. P., and B. T. Korber. 2000. Detecting hypermutations in viral sequences with an emphasis on G ->A hypermutation. Bioinformatics 16:400-401.[Abstract/Free Full Text]
    24. 24
  24. Saitou, N., and M. Nei. 1987. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol. 4:406-425.[Abstract]
    25. 25
  25. Schrofelbauer, B., D. Chen, and N. R. Landau. 2004. A single amino acid of APOBEC3G controls its species-specific interaction with virion infectivity factor (Vif). Proc. Natl. Acad. Sci. USA 101:3927-3932.[Abstract/Free Full Text]
    26. 26
  26. Sheehy, A. M., N. C. Gaddis, J. D. Choi, and M. H. Malim. 2002. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418:646-650.[CrossRef][Medline]
    27. 27
  27. Sheehy, A. M., N. C. Gaddis, and M. H. Malim. 2003. The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nat. Med. 9:1404-1407.[CrossRef][Medline]
    28. 28
  28. Siliciano, J. D., J. Kajdas, D. Finzi, T. C. Quinn, K. Chadwick, J. B. Margolick, C. Kovacs, S. J. Gange, and R. F. Siliciano. 2003. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat. Med. 9:727-728.[CrossRef][Medline]
    29. 29
  29. Simon, J. H., and M. H. Malim. 1996. The human immunodeficiency virus type 1 Vif protein modulates the postpenetration stability of viral nucleoprotein complexes. J. Virol. 70:5297-5305.[Abstract/Free Full Text]
    30. 30
  30. Stopak, K., C. de Noronha, W. Yonemoto, and W. C. Greene. 2003. HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability. Mol. Cell 12:591-601.[CrossRef][Medline]
    31. 31
  31. Vartanian, J. P., A. Meyerhans, B. Asjo, and S. Wain-Hobson. 1991. Selection, recombination, and G->A hypermutation of human immunodeficiency virus type 1 genomes. J. Virol. 65:1779-1788.[Abstract/Free Full Text]
    32. 32
  32. von Schwedler, U., J. Song, C. Aiken, and D. Trono. 1993. Vif is crucial for human immunodeficiency virus type 1 proviral DNA synthesis in infected cells. J. Virol. 67:4945-4955.[Abstract/Free Full Text]
    33. 33
  33. Wiegand, H. L., B. P. Doehle, H. P. Bogerd, and B. R. Cullen. 2004. A second human antiretroviral factor, APOBEC3F, is suppressed by the HIV-1 and HIV-2 Vif proteins. EMBO J. 23:2451-2458.[CrossRef][Medline]
    34. 34
  34. Xu, H., E. S. Svarovskaia, R. Barr, Y. Zhang, M. A. Khan, K. Strebel, and V. K. Pathak. 2004. A single amino acid substitution in human APOBEC3G antiretroviral enzyme confers resistance to HIV-1 virion infectivity factor-induced depletion. Proc. Natl. Acad. Sci. USA 101:5652-5657.[Abstract/Free Full Text]
    35. 35
  35. Yu, Q., R. Konig, S. Pillai, K. Chiles, M. Kearney, S. Palmer, D. Richman, J. M. Coffin, and N. R. Landau. 2004. Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome. Nat. Struct. Mol. Biol. 11:435-442.[CrossRef][Medline]
    36. 36
  36. Zhang, H., B. Yang, R. J. Pomerantz, C. Zhang, S. C. Arunachalam, and L. Gao. 2003. The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature 424:94-98.[CrossRef][Medline]

Journal of Virology, February 2005, p. 1975-1980, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1975-1980.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Koning, F. A., Newman, E. N. C., Kim, E.-Y., Kunstman, K. J., Wolinsky, S. M., Malim, M. H. (2009). Defining APOBEC3 Expression Patterns in Human Tissues and Hematopoietic Cell Subsets. J. Virol. 83: 9474-9485 [Abstract] [Full Text]  
  • Piantadosi, A., Humes, D., Chohan, B., McClelland, R. S., Overbaugh, J. (2009). Analysis of the Percentage of Human Immunodeficiency Virus Type 1 Sequences That Are Hypermutated and Markers of Disease Progression in a Longitudinal Cohort, Including One Individual with a Partially Defective Vif. J. Virol. 83: 7805-7814 [Abstract] [Full Text]  
  • Malim, M. H (2009). APOBEC proteins and intrinsic resistance to HIV-1 infection. Phil Trans R Soc B 364: 675-687 [Abstract] [Full Text]  
  • Petit, V., Vartanian, J.-P., Wain-Hobson, S. (2009). Powerful mutators lurking in the genome. Phil Trans R Soc B 364: 705-715 [Abstract] [Full Text]  
  • Armitage, A. E., Katzourakis, A., de Oliveira, T., Welch, J. J., Belshaw, R., Bishop, K. N., Kramer, B., McMichael, A. J., Rambaut, A., Iversen, A. K. N. (2008). Conserved Footprints of APOBEC3G on Hypermutated Human Immunodeficiency Virus Type 1 and Human Endogenous Retrovirus HERV-K(HML2) Sequences. J. Virol. 82: 8743-8761 [Abstract] [Full Text]  
  • Land, A. M., Ball, T. B., Luo, M., Pilon, R., Sandstrom, P., Embree, J. E., Wachihi, C., Kimani, J., Plummer, F. A. (2008). Human Immunodeficiency Virus (HIV) Type 1 Proviral Hypermutation Correlates with CD4 Count in HIV-Infected Women from Kenya. J. Virol. 82: 8172-8182 [Abstract] [Full Text]  
  • Knoepfel, S. A., Salisch, N. C., Huelsmann, P. M., Rauch, P., Walter, H., Metzner, K. J. (2008). Comparison of G-to-A Mutation Frequencies Induced by APOBEC3 Proteins in H9 Cells and Peripheral Blood Mononuclear Cells in the Context of Impaired Processivities of Drug-Resistant Human Immunodeficiency Virus Type 1 Reverse Transcriptase Variants. J. Virol. 82: 6536-6545 [Abstract] [Full Text]  
  • Mulder, L. C. F., Harari, A., Simon, V. (2008). Cytidine deamination induced HIV-1 drug resistance. Proc. Natl. Acad. Sci. USA 105: 5501-5506 [Abstract] [Full Text]  
  • Gandhi, S. K., Siliciano, J. D., Bailey, J. R., Siliciano, R. F., Blankson, J. N. (2008). Role of APOBEC3G/F-Mediated Hypermutation in the Control of Human Immunodeficiency Virus Type 1 in Elite Suppressors. J. Virol. 82: 3125-3130 [Abstract] [Full Text]  
  • Aguiar, R. S., Lovsin, N., Tanuri, A., Peterlin, B. M. (2008). Vpr.A3A Chimera Inhibits HIV Replication. J. Biol. Chem. 283: 2518-2525 [Abstract] [Full Text]  
  • Gallois-Montbrun, S., Kramer, B., Swanson, C. M., Byers, H., Lynham, S., Ward, M., Malim, M. H. (2007). Antiviral Protein APOBEC3G Localizes to Ribonucleoprotein Complexes Found in P Bodies and Stress Granules. J. Virol. 81: 2165-2178 [Abstract] [Full Text]  
  • Holmes, R. K., Koning, F. A., Bishop, K. N., Malim, M. H. (2007). APOBEC3F Can Inhibit the Accumulation of HIV-1 Reverse Transcription Products in the Absence of Hypermutation: COMPARISONS WITH APOBEC3G. J. Biol. Chem. 282: 2587-2595 [Abstract] [Full Text]  
  • Bishop, K. N., Holmes, R. K., Malim, M. H. (2006). Antiviral Potency of APOBEC Proteins Does Not Correlate with Cytidine Deamination.. J. Virol. 80: 8450-8458 [Abstract] [Full Text]  
  • Pace, C., Keller, J., Nolan, D., James, I., Gaudieri, S., Moore, C., Mallal, S. (2006). Population Level Analysis of Human Immunodeficiency Virus Type 1 Hypermutation and Its Relationship with APOBEC3G and vif Genetic Variation.. J. Virol. 80: 9259-9269 [Abstract] [Full Text]  
  • Bailey, J. R., Sedaghat, A. R., Kieffer, T., Brennan, T., Lee, P. K., Wind-Rotolo, M., Haggerty, C. M., Kamireddi, A. R., Liu, Y., Lee, J., Persaud, D., Gallant, J. E., Cofrancesco, J. Jr., Quinn, T. C., Wilke, C. O., Ray, S. C., Siliciano, J. D., Nettles, R. E., Siliciano, R. F. (2006). 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. 80: 6441-6457 [Abstract] [Full Text]  
  • Bailey, J. R., Williams, T. M., Siliciano, R. F., Blankson, J. N. (2006). Maintenance of viral suppression in HIV-1-infected HLA-B*57+ elite suppressors despite CTL escape mutations. JEM 203: 1357-1369 [Abstract] [Full Text]  
  • Bailey, J. R., Lassen, K. G., Yang, H.-C., Quinn, T. C., Ray, S. C., Blankson, J. N., Siliciano, R. F. (2006). Neutralizing antibodies do not mediate suppression of human immunodeficiency virus type 1 in elite suppressors or selection of plasma virus variants in patients on highly active antiretroviral therapy.. J. Virol. 80: 4758-4770 [Abstract] [Full Text]  
  • Swiggard, W. J., Baytop, C., Yu, J. J., Dai, J., Li, C., Schretzenmair, R., Theodosopoulos, T., O'Doherty, U. (2005). Human Immunodeficiency Virus Type 1 Can Establish Latent Infection in Resting CD4+ T Cells in the Absence of Activating Stimuli. J. Virol. 79: 14179-14188 [Abstract] [Full Text]  
  • Nettles, R. E., Kieffer, T. L., Kwon, P., Monie, D., Han, Y., Parsons, T., Cofrancesco, J. Jr, Gallant, J. E., Quinn, T. C., Jackson, B., Flexner, C., Carson, K., Ray, S., Persaud, D., Siliciano, R. F. (2005). Intermittent HIV-1 Viremia (Blips) and Drug Resistance in Patients Receiving HAART. JAMA 293: 817-829 [Abstract] [Full Text]  

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kieffer, T. L.
Right arrow Articles by Siliciano, R. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kieffer, T. L.
Right arrow Articles by Siliciano, R. F.

Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»