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HIV

Driving HIV out of hiding

Nature Reviews Immunology volume 4, page 749 (2004)Cite this article

The authors used DNA microarrays to study gene expression in cell lines that were chronically infected with HIV, both before and during activation of lytic infection with phorbol myristate acetate, and they compared these cells with uninfected control cells. Activation of the lytic cycle and production of virus was confirmed by measuring the expression of the late HIV protein p24 by flow cytometry. Several differences in gene expression were observed between chronically infected cells and uninfected cells, and these genes could have a role in the maintenance of latency. Several genes that encode proteasome subunits and histone deacetylases were upregulated before lytic induction, and other genes were downregulated, including EGR1 (which is involved in cell-cycle regulation), CDC42 (a RHO-family GTPase) and the tyrosine kinase LYN.

The authors reasoned that by targeting genes that are both differentially expressed and possibly important for latency, they could drive the virus out of latency into the lytic cycle. To test this, they targeted the proteasome subunits and EGR1 because specific agents were available to target these molecules. Treating latently infected cells with a proteasome inhibitor or an EGR1 activator induced dose-dependent increases in p24 expression, showing that viral reactivation had occurred — although the exact mechanisms by which these molecules end latency needs further study. The authors also identified several cellular genes that were differentially expressed during active viral replication — targeting these genes might therefore inhibit viral replication.

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References

ORIGINAL RESEARCH PAPER

  1. Krishnan, V. & Zeichner, S. L. Host cell gene expression during human immunodeficiency virus type 1 latency and reactivation and effects of targeting genes that are differentially expressed in viral latency. J. Virol. 78, 9458–9473 (2004).

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FURTHER READING

  1. Hamer, D. H. Can HIV be cured? Mechanisms of HIV persistence and strategies to combat it. Curr. HIV Res. 2, 99–111 (2004).

    Article  CAS  Google Scholar 

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Authors
  1. Elaine Bell
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Bell, E. Driving HIV out of hiding. Nat Rev Immunol 4, 749 (2004). https://doi.org/10.1038/nri1467

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  • DOI: https://doi.org/10.1038/nri1467

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