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Naturally occurring accessory gene mutations lead to persistent human immunodeficiency virus type 1 infection of

M Kishi1, Y H Zheng, M K Bahmani

  • 1Section of Serology, Hokkaido University, Sapporo, Japan.

Journal of Virology
|December 1, 1995
PubMed

Insights

Mutations in human immunodeficiency virus type 1 (HIV-1) accessory genes, such as vif, vpr, and vpu, lead to large deletions and frameshifts. These genetic defects correlate with viral persistence and reduced cytopathogenicity.

Area of Science:

  • Virology
  • Molecular Biology
  • Genetics

Background:

  • Recombinant human immunodeficiency virus type 1 (HIV-1) can cause severe cytopathic effects.
  • Accessory genes like vif, vpr, and vpu play roles in HIV-1 replication and pathogenicity.

Purpose of the Study:

  • To characterize proviral DNA in cells surviving HIV-1 infection with mutations in accessory genes.
  • To investigate the mechanisms generating mutations during HIV-1 replication.
  • To determine the correlation between accessory gene mutations and viral cytopathogenicity.

Main Methods:

  • Two-step PCR using HIV-1-specific primers to analyze proviral DNA.
  • Cloning and sequencing of amplified DNA regions.
  • Analysis of deletion patterns and potential mutation mechanisms.

Main Results:

  • Large deletions were frequently observed in the vif and vpr open reading frames.
  • Mechanisms such as genetic recombination, template-primer slippage, and reverse transcription misalignment were suggested.
  • Smaller frameshift mutations in vif and/or vpr were prevalent.
  • A triple mutant defective in vif, vpr, and vpu showed no cytopathic effect.

Conclusions:

  • Mutations leading to multiple accessory gene defects in HIV-1 are associated with viral persistence.
  • Loss of cytopathogenicity in HIV-1 correlates with defects in accessory genes like vif, vpr, and vpu.

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