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Fate-Regulating Circuits in Viruses: From Discovery to New Therapy Targets

Anand Pai1, Leor S Weinberger1,2

  • 1Gladstone Institute of Virology and Immunology, San Francisco, California 94158;

Annual Review of Virology
|August 12, 2017
PubMed

Insights

New antivirals targeting viral master circuits could overcome resistance. These circuits control viral activity, offering a novel strategy for durable therapies against viruses like HIV-1 and herpesviruses.

Area of Science:

  • Virology
  • Molecular Biology
  • Drug Discovery

Background:

  • Current antiviral therapies face challenges with viral latency and resistance.
  • Pathogens like human immunodeficiency virus type 1 (HIV-1) and herpesviruses remain difficult to cure.
  • Viral latency and drug resistance limit the effectiveness of existing treatments.

Purpose of the Study:

  • To review the discovery and significance of viral master circuits.
  • To explore the potential of targeting these circuits for novel antiviral therapies.
  • To discuss strategies for developing escape-resistant treatments against persistent viral infections.

Main Methods:

  • Review of existing literature on viral gene networks and regulatory circuits.
  • Analysis of master circuit architectures in HIV-1 and human herpesvirus cytomegalovirus (CMV).
  • Exploration of potential strategies to disrupt viral master circuits.

Main Results:

  • Viral master circuits are virus-encoded autoregulatory gene networks controlling viral expression fates (active, latent, abortive).
  • Disrupting these circuits offers a new class of antivirals with intrinsic combination therapy potential.
  • Simultaneous evolution of cis and trans elements is required for viral escape from circuit-disrupting antivirals.

Conclusions:

  • Viral master circuits represent a promising target for developing novel antiviral strategies.
  • Targeting these circuits may lead to therapies that are more resistant to viral evolution and escape.
  • This approach holds potential for achieving curative therapies against challenging viruses like HIV-1 and CMV.
Keywords:
CMVHIVautoregulatory circuitsfate regulationfeedbacklatencystochastic noisetranscriptiontranscriptional fluctuations

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