The RNA binding G-patch domain in retroviral protease is important for infectivity and D-type morphogenesis of

Helena Bauerová-Zábranská1, Jitka Stokrová, Kvido Strísovsky

  • 1Centre for New Antivirals and Antineoplastics, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague.

Insights

The G-patch domain of Mason-Pfizer monkey virus protease is not essential for polyprotein processing but is critical for M-PMV infectivity and reverse transcriptase activity.

Area of Science:

  • Virology
  • Molecular Biology
  • Structural Biology

Background:

  • Retroviral proteases (PRs) are vital for viral replication, cleaving polyproteins into mature proteins.
  • Beta-retroviruses, like M-PMV, exhibit unique cytoplasmic capsid assembly and regulated protease activation.
  • Unique C-terminal G-patch motifs in beta-retroviral PRs bind nucleic acids and are autoproteolytically processed.

Purpose of the Study:

  • To investigate the role of the G-patch domain in the M-PMV protease (PR) on the virus life cycle.
  • To determine the necessity of the G-patch for polyprotein processing and viral infectivity.
  • To elucidate the impact of G-patch mutations on M-PMV assembly and reverse transcriptase activity.

Main Methods:

  • Site-directed mutagenesis was used to introduce mutations within the C-terminal domain of M-PMV PR.
  • Analysis of viral polyprotein processing in cells expressing mutated M-PMV PR.
  • Assessment of M-PMV infectivity, reverse transcriptase activity, and capsid assembly in the presence of mutations.

Main Results:

  • The G-patch domain of M-PMV PR is not required for viral polyprotein processing.
  • Mutations in the G-patch domain significantly affected M-PMV infectivity.
  • The G-patch domain influences reverse transcriptase activity and immature capsid assembly within cells.

Conclusions:

  • The G-patch domain of M-PMV PR is critical for the beta-retrovirus life cycle.
  • The evolutionary conservation of the G-patch suggests its importance for D-type morphology retroviruses.
  • This study highlights a novel regulatory role for the G-patch in M-PMV replication.

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