CoChat
Sign Up
Cited by 155HIV Research and TreatmentVirus-based gene therapy researchT-cell and Retrovirus Studies

24 hours in the life of HIV-1 in a T cell line

Open access
Mohammadi, Pejman, Desfarges, Sébastien, Bartha, István, Joos, Beda, Zangger, Nadine, Muñoz, Miguel, Günthard, Huldrych F., Beerenwinkel, Niko +2 more·2013·PLoS Pathogens
DOI 10.1371/journal.ppat.1003161PMC PMC3561177
Open this paper in CoChat — free accountOpen PDF

Abstract

HIV-1 infects CD4+ T cells and completes its replication cycle in approximately 24 hours. We employed repeated measurements in a standardized cell system and rigorous mathematical modeling to characterize the emergence of the viral replication intermediates and their impact on the cellular transcriptional response with high temporal resolution. We observed 7,991 (73%) of the 10,958 expressed genes to be modulated in concordance with key steps of viral replication. Fifty-two percent of the overall variability in the host transcriptome was explained by linear regression on the viral life cycle. This profound perturbation of cellular physiology was investigated in the light of several regulatory mechanisms, including transcription factors, miRNAs, host-pathogen interaction, and proviral integration. Key features were validated in primary CD4+ T cells, and with viral constructs using alternative entry strategies. We propose a model of early massive cellular shutdown and progressive upregulation of the cellular machinery to complete the viral life cycle.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.ppat.1003161

Cites

5 of 5 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • mRNA levels of some tRNA synthetases are altered in CD4+ T-cells infected with HIV-1.

    “The observation that mRNA levels of some tRNA synthetases are altered in CD4 ϩ T-cells infected with HIV-1 (Table 1) suggests a delicate arms race between viral infection and expression of these synthetases (128).”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [128]

    The Results/Discussion section on host transcriptome changes (page unavailable) includes tRNA synthetases among the gene groups downregulated after HIV-vector infection of the SupT1 T-cell line. The paper also tests selected genes in primary CD4+ T cells, but the passages do not establish that tRNA-synthetase mRNA levels were altered in those primary cells. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • A transcriptome-wide study of T-cells infected with HIV-1 revealed a series of host transcripts affected by viral infection.

    “A transcriptome-wide study of T-cells infected with HIV-1 revealed a series of host transcripts affected by viral infection (128).”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [128]

  • The alteration of mRNA levels of some tRNA synthetases in HIV-1-infected CD4+ T-cells suggests a delicate arms race between viral infection and expression of these synthetases.

    “The observation that mRNA levels of some tRNA synthetases are altered in CD4 ϩ T-cells infected with HIV-1 (Table 1) suggests a delicate arms race between viral infection and expression of these synthetases (128).”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [128]

  • siRNA depletion of LysRS and LeuRS decreases HIV-1 replication.

    “siRNA depletion decreases HIV-1 replication LysRS a , LeuRS a”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [128]

    The Results/Discussion section on host transcriptome changes (page unavailable) reports that HIV infection downregulated genes encoding tRNA synthetases; it does not report siRNA depletion of LysRS or LeuRS. Searches for both synthetases and for knockdown effects found no passage linking their depletion to decreased HIV-1 replication. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • LysRS and IleRS are packaged in HIV-1 virions.

    “| Packaged in HIV-1 virion | LysRS a , IleRS a | 12, 128 |”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [128]

    The Materials and Methods section on virus production describes how viral particles were prepared, but does not identify LysRS or IleRS as virion components. Searches for both protein names and their full names found no passage in our copy addressing their packaging in HIV-1 virions. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 24

  1. [1]Bushman FD, Nabel GJ, Swanstrom R (2012) HIV - from biology to prevention and treatment; Bushman FD, Nabel GJ, Swanstrom R, editors. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press. 572 p.
  2. [2]Mehla R, Ayyavoo V (2012) Gene array studies in HIV-1 infection. Curr HIV/AIDS Rep 9: 34– 43. 22184032 PMC3968537
  3. [4]Imbeault M, Giguere K, Ouellet M, Tremblay MJ (2012) Exon Level Transcriptomic Profiling of HIV-1-Infected CD4(+) T Cells Reveals Virus-Induced Genes and Host Environment Favorable for Viral Replication. PLoS Pathog 8: e1002861. 22876188 PMC3410884
  4. [5]Lefebvre G, Desfarges S, Uyttebroeck F, Muñoz M, Beerenwinkel N, et al (2011) Analysis of HIV-1 expression level and sense of transcription by high-throughput sequencing of the infected cell. J Virol 85: 6205– 6211. 21507965 PMC3126515
  5. [7]Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, et al (2011) A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 472: 481– 485. 21478870 PMC3409588
  6. [10]Konig R, Zhou Y, Elleder D, Diamond TL, Bonamy GM, et al (2008) Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell 135: 49– 60. 18854154 PMC2628946
  7. [11]Zhou H, Xu M, Huang Q, Gates AT, Zhang XD, et al (2008) Genome-scale RNAi screen for host factors required for HIV replication. Cell Host Microbe 4: 495– 504. 18976975
  8. [12]Yeung ML, Houzet L, Yedavalli VS, Jeang KT (2009) A genome-wide short hairpin RNA screening of jurkat T-cells for human proteins contributing to productive HIV-1 replication. J Biol Chem 284: 19463– 19473. 19460752 PMC2740572
  9. [13]Chatr-aryamontri A, Ceol A, Peluso D, Nardozza A, Panni S, et al (2009) VirusMINT: a viral protein interaction database. Nucleic Acids Res 37: D669– 673. 18974184 PMC2686573
  10. [14]Houzet L, Jeang KT (2011) MicroRNAs and human retroviruses. Biochim Biophys Acta 1809: 686– 693. 21640212 PMC3177989
  11. [15]Desfarges S, Ciuffi A (2010) Retroviral integration site selection. Viruses 2: 111– 130. 21994603 PMC3185549
  12. [16]The International AIDS Society Scientific Working Group on HIV Cure (2012) “Towards an HIV Cure”: a global scientific strategy. Nat Rev Immunol 12: 607– 614. 22814509 PMC3595991
  13. [17]Zhang H, Zhou Y, Alcock C, Kiefer T, Monie D, et al (2004) Novel single-cell-level phenotypic assay for residual drug susceptibility and reduced replication capacity of drug-resistant human immunodeficiency virus type 1. J Virol 78: 1718– 1729. 14747537 PMC369469
  14. [19]Schmid A, Gianella S, von Wyl V, Metzner KJ, Scherrer AU, et al (2010) Profound depletion of HIV-1 transcription in patients initiating antiretroviral therapy during acute infection. PLoS ONE 5: e13310. 20967271 PMC2953504
  15. [20]Langmead B, Trapnell C, Pop M, Salzberg SL (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10: R25. 19261174 PMC2690996
  16. [21]Wu ZJ, Meyer CA, Choudhury S, Shipitsin M, Maruyama R, et al (2010) Gene expression profiling of human breast tissue samples using SAGE-Seq. Genome Res 20: 1730– 1739. 21045080 PMC2989999
  17. [22]Anders S, Huber W (2010) Differential expression analysis for sequence count data. Genome Biol 11: R106. 20979621 PMC3218662
  18. [23]Morgulis A, Coulouris G, Raytselis Y, Madden TL, Agarwala R, et al (2008) Database indexing for production MegaBLAST searches. Bioinformatics 24: 1757– 1764. 18567917 PMC2696921
  19. [24]Kozomara A, Griffiths-Jones S (2011) miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 39: D152– 157. 21037258 PMC3013655
  20. [29]Vergoulis T, Vlachos IS, Alexiou P, Georgakilas G, Maragkakis M, et al (2012) TarBase 6.0: capturing the exponential growth of miRNA targets with experimental support. Nucleic Acids Res 40: D222– 229. 22135297 PMC3245116
  21. [31]Ciuffi A, Barr SD (2011) Identification of HIV integration sites in infected host genomic DNA. Methods 53: 39– 46. 20385239
  22. [32]Wang GP, Ciuffi A, Leipzig J, Berry CC, Bushman FD (2007) HIV integration site selection: analysis by massively parallel pyrosequencing reveals association with epigenetic modifications. Genome Res 17: 1186– 1194. 17545577 PMC1933515
  23. [33]Brussel A, Delelis O, Sonigo P (2005) Alu-LTR real-time nested PCR assay for quantifying integrated HIV-1 DNA. Methods Mol Biol 304: 139– 154. 16061972
  24. [34]Yang HC, Xing S, Shan L, O'Connell K, Dinoso J, et al (2009) Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation. J Clin Invest 119: 3473– 3486. 19805909 PMC2769176

Cited by

Sorted by citations

Authors
Mohammadi, P., Desfarges, S., Bartha, I., Joos, B., Zangger, N., Muñoz, M., Günthard, H. F., Beerenwinkel, N., Telenti, A., & Ciuffi, A.
Affiliations
  • SIB Swiss Institute of Bioinformatics (CH)
  • Centre Hospitalier Universitaire Vaudois (CH)
  • University of Zurich (CH)
Corresponding author
  • Beerenwinkel, Niko
  • Telenti, Amalio
  • Ciuffi, Angela
ORCID
Venue
PLoS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2013-01-31
Volume
9
Issue
1
Pages
e1003161
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1003161
PMC
PMC3561177
OpenAlex
W2058426539
Cited by
155
References
5
Citations by year
2026: 8 · 2025: 2 · 2024: 8 · 2023: 15 · 2022: 6 · 2021: 15 · 2020: 13 · 2019: 16 · 2018: 14 · 2017: 12 · 2016: 16 · 2015: 16 · 2014: 8 · 2013: 6
FWCI
7.04
Type
journal article
Language
en
Update notices
correction (2015-06-15)
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
  • IRIS (submittedVersion)
  • Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • SERVAL (Université de Lausanne) (submittedVersion, other-oa)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
  • ETH Zürich Research Collection (cc-by)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • National Science Foundation (310030)
  • Bill and Melinda Gates Foundation
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (127317, 130699, 310030)
  • National Institutes of Health (pNL4-3)
  • National Institute of Allergy and Infectious Diseases (pNL4-3)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
Keywords
HIV-1, CD4+ T cells, viral life cycle, host transcriptome, host-pathogen interaction, transcription factors, microRNA, proviral integration, primary T cells
MeSH terms
Humans, Time Factors, Virus Replication, Models, Statistical, CD4-Positive T-Lymphocytes, HIV-1, Up-Regulation, Gene Expression Regulation, Viral, Host-Pathogen Interactions, HEK293 Cells, Transcriptome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review