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HIV-1 transcripts use IRES-initiation under conditions where Cap-dependent translation is restricted by poliovirus 2A

Raquel Amorim1, Sara Mesquita Costa1, Nathalia Pereira Cavaleiro1

  • 1Instituto de Microbiologia, Departamento de Virologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Plos One
|February 13, 2014
PubMed

Insights

Poliovirus 2A protease inhibits HIV-1 protein synthesis by blocking cap-dependent translation. This reveals two distinct translation mechanisms driving HIV-1 replication, with IRES-driven translation becoming dominant later in infection.

Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Biology

Background:

  • Human Immunodeficiency Virus type 1 (HIV-1) replication involves synthesizing numerous mRNA species.
  • Cap-dependent translation is considered the primary mechanism for initiating HIV-1 protein synthesis.
  • Internal Ribosome Entry Sites (IRES) in HIV-1 mRNA suggest alternative translation initiation pathways.

Purpose of the Study:

  • To investigate the role of cap-dependent translation in HIV-1 protein synthesis.
  • To explore the impact of poliovirus 2A protease on HIV-1 replication.
  • To elucidate the contribution of different translation initiation mechanisms during HIV-1 infection.

Main Methods:

  • Utilized a cell system with transient expression of poliovirus 2A protease.
  • Assessed the effect of varying protease levels on cellular cap-dependent translation.
  • Monitored HIV-1 protein synthesis, viral production, and infectivity over time.

Main Results:

  • Poliovirus 2A protease inhibited cellular cap-dependent translation without toxicity.
  • HIV-1 protein synthesis was temporally and dose-dependently inhibited by the protease.
  • Higher protease levels severely inhibited early viral protein synthesis and production; lower levels caused transient inhibition, with later recovery of protein synthesis and viral release but partial loss of infectivity.

Conclusions:

  • HIV-1 protein synthesis relies on both cap-dependent and IRES-driven translation.
  • Cap-dependent translation is crucial during the initial 24-48 hours of HIV-1 replication.
  • IRES-driven translation becomes sufficient for high viral particle production at later stages.

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