This Article
Right arrow Full Text
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 Janini, M.
Right arrow Articles by McCutchan, F. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Janini, M.
Right arrow Articles by McCutchan, F. E.

 Previous Article  |  Next Article 

Journal of Virology, September 2001, p. 7973-7986, Vol. 75, No. 17
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.17.7973-7986.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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

Mario Janini,1,* Melissa Rogers,1 Deborah R. Birx,2 and Francine E. McCutchan1

Henry M. Jackson Foundation, Rockville, Maryland 20850,1 and Walter Reed Army Institute of Research, Washington, D.C.2

Received 26 March 2001/Accepted 4 June 2001

G-to-A hypermutation has been sporadically observed in human immunodeficiency virus type 1 (HIV-1) proviral sequences from patient peripheral blood mononuclear cells (PBMC) and virus cultures but has not been systematically evaluated. PCR primers matched to normal and hypermutated sequences were used in conjunction with an agarose gel electrophoresis system incorporating an AT-binding dye to visualize, separate, clone, and sequence hypermutated and normal sequences in the 297-bp HIV-1 protease gene amplified from patient PBMC. Among 53 patients, including individuals infected with subtypes A through D and at different clinical stages, at least 43% of patients harbored abundant hypermutated, along with normal, protease genes. In 70 hypermutated sequences, saturation of G residues in the GA or GG dinucleotide context ranged from 20 to 94%. Levels of other mutants were not elevated, and G-to-A replacement was entirely restricted to GA or GG, and not GC or GT, dinucleotides. Sixty-nine of 70 hypermutated and 3 of 149 normal sequences had in-frame stop codons. To investigate the conditions under which hypermutation occurs in cell cultures, purified CD4+ T cells from normal donors were infected with cloned NL4-3 virus stocks at various times before and after phytohemagglutinin (PHA) activation. Hypermutation was pronounced when HIV-1 infection occurred simultaneously with, or a few hours after, PHA activation, but after 12 h or more after PHA activation, most HIV-1 sequences were normal. Hypermutated sequences generated in culture corresponded exactly in all parameters to those obtained from patient PBMC. Near-simultaneous activation and infection of CD4+ T cells may represent a window of susceptibility where the informational content of HIV-1 sequences is lost due to hypermutation.

* Corresponding author. Mailing address: Henry M. Jackson Foundation, 1 Taft Ct., Rockville, MD 20850. Phone: (301) 251-5064. Fax: (301) 294-1898. E-mail: mjanini{at}hivresearch.org.

Journal of Virology, September 2001, p. 7973-7986, Vol. 75, No. 17
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.17.7973-7986.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Langlois, M.-A., Kemmerich, K., Rada, C., Neuberger, M. S. (2009). The AKV Murine Leukemia Virus Is Restricted and Hypermutated by Mouse APOBEC3. J. Virol. 83: 11550-11559 [Abstract] [Full Text]  
  • 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]  
  • Henriet, S., Mercenne, G., Bernacchi, S., Paillart, J.-C., Marquet, R. (2009). Tumultuous Relationship between the Human Immunodeficiency Virus Type 1 Viral Infectivity Factor (Vif) and the Human APOBEC-3G and APOBEC-3F Restriction Factors. Microbiol. Mol. Biol. Rev. 73: 211-232 [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]  
  • Chiu, Y.-L., Greene, W. C (2009). APOBEC3G: an intracellular centurion. Phil Trans R Soc B 364: 689-703 [Abstract] [Full Text]  
  • Lee, Y. N., Malim, M. H., Bieniasz, P. D. (2008). Hypermutation of an Ancient Human Retrovirus by APOBEC3G. J. Virol. 82: 8762-8770 [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]  
  • 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]  
  • Schneidewind, A., Brockman, M. A., Sidney, J., Wang, Y. E., Chen, H., Suscovich, T. J., Li, B., Adam, R. I., Allgaier, R. L., Mothe, B. R., Kuntzen, T., Oniangue-Ndza, C., Trocha, A., Yu, X. G., Brander, C., Sette, A., Walker, B. D., Allen, T. M. (2008). Structural and Functional Constraints Limit Options for Cytotoxic T-Lymphocyte Escape in the Immunodominant HLA-B27-Restricted Epitope in Human Immunodeficiency Virus Type 1 Capsid. J. Virol. 82: 5594-5605 [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]  
  • 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]  
  • Noguchi, C., Hiraga, N., Mori, N., Tsuge, M., Imamura, M., Takahashi, S., Fujimoto, Y., Ochi, H., Abe, H., Maekawa, T., Yatsuji, H., Shirakawa, K., Takaori-Kondo, A., Chayama, K. (2007). Dual effect of APOBEC3G on Hepatitis B virus. J. Gen. Virol. 88: 432-440 [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., 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]  
  • Cullen, B. R. (2006). Role and Mechanism of Action of the APOBEC3 Family of Antiretroviral Resistance Factors. J. Virol. 80: 1067-1076 [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]  
  • Mahieux, R., Suspene, R., Delebecque, F., Henry, M., Schwartz, O., Wain-Hobson, S., Vartanian, J.-P. (2005). Extensive editing of a small fraction of human T-cell leukemia virus type 1 genomes by four APOBEC3 cytidine deaminases. J. Gen. Virol. 86: 2489-2494 [Abstract] [Full Text]  
  • Jin, X., Brooks, A., Chen, H., Bennett, R., Reichman, R., Smith, H. (2005). APOBEC3G/CEM15 (hA3G) mRNA Levels Associate Inversely with Human Immunodeficiency Virus Viremia. J. Virol. 79: 11513-11516 [Abstract] [Full Text]  
  • Schumacher, A. J., Nissley, D. V., Harris, R. S. (2005). APOBEC3G hypermutates genomic DNA and inhibits Ty1 retrotransposition in yeast. Proc. Natl. Acad. Sci. USA 102: 9854-9859 [Abstract] [Full Text]  
  • Suspene, R., Guetard, D., Henry, M., Sommer, P., Wain-Hobson, S., Vartanian, J.-P. (2005). Extensive editing of both hepatitis B virus DNA strands by APOBEC3 cytidine deaminases in vitro and in vivo. Proc. Natl. Acad. Sci. USA 102: 8321-8326 [Abstract] [Full Text]  
  • Langlois, M.-A., Beale, R. C. L., Conticello, S. G., Neuberger, M. S. (2005). Mutational comparison of the single-domained APOBEC3C and double-domained APOBEC3F/G anti-retroviral cytidine deaminases provides insight into their DNA target site specificities. Nucleic Acids Res 33: 1913-1923 [Abstract] [Full Text]  
  • Kieffer, T. L., Kwon, P., Nettles, R. E., Han, Y., Ray, S. C., Siliciano, R. F. (2005). G->A Hypermutation in Protease and Reverse Transcriptase Regions of Human Immunodeficiency Virus Type 1 Residing in Resting CD4+ T Cells In Vivo. J. Virol. 79: 1975-1980 [Abstract] [Full Text]  
  • Suspene, R., Henry, M., Guillot, S., Wain-Hobson, S., Vartanian, J.-P. (2005). Recovery of APOBEC3-edited human immunodeficiency virus G->A hypermutants by differential DNA denaturation PCR. J. Gen. Virol. 86: 125-129 [Abstract] [Full Text]  
  • Pastore, C., Ramos, A., Mosier, D. E. (2004). Intrinsic Obstacles to Human Immunodeficiency Virus Type 1 Coreceptor Switching. J. Virol. 78: 7565-7574 [Abstract] [Full Text]  
  • Suspene, R., Sommer, P., Henry, M., Ferris, S., Guetard, D., Pochet, S., Chester, A., Navaratnam, N., Wain-Hobson, S., Vartanian, J.-P. (2004). APOBEC3G is a single-stranded DNA cytidine deaminase and functions independently of HIV reverse transcriptase. Nucleic Acids Res 32: 2421-2429 [Abstract] [Full Text]  
  • Tang, Y., Villinger, F., Staprans, S. I., Amara, R. R., Smith, J. M., Herndon, J. G., Robinson, H. L. (2002). Slowly Declining Levels of Viral RNA and DNA in DNA/Recombinant Modified Vaccinia Virus Ankara-Vaccinated Macaques with Controlled Simian-Human Immunodeficiency Virus SHIV-89.6P Challenges. J. Virol. 76: 10147-10154 [Abstract] [Full Text]  
  • Vartanian, J.-P., Henry, M., Wain-Hobson, S. (2002). Sustained G->A hypermutation during reverse transcription of an entire human immunodeficiency virus type 1 strain Vau group O genome. J. Gen. Virol. 83: 801-805 [Abstract] [Full Text]  


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