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Related Experiment Videos

Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are Consistent with Intersubtype Differences

Marion W Kiguoya1,2, Jaclyn K Mann1,2, Denis Chopera2,3

  • 1HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.

Journal of Virology
|April 21, 2017
PubMed

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Summary

HIV-1 Gag-protease replication capacity varies by subtype, influencing disease progression. Lower replication in subtypes A and C may paradoxically increase their global prevalence.

Area of Science:

  • Virology
  • Immunology
  • Epidemiology

Background:

  • Significant global variations exist in Human Immunodeficiency Virus type 1 (HIV-1) subtype spread and prevalence.
  • Reported differences in clinical progression among HIV-1 subtypes suggest underlying biological determinants, which remain largely unknown.
  • The Gag-protease component is crucial for HIV-1 replication, and its replication capacity has been linked to disease progression.

Purpose of the Study:

  • To investigate the correlation between Gag-protease replication capacity and overall viral isolate replication capacity.
  • To explore subtype-specific differences in Gag-protease-driven replication capacity.
  • To identify genetic determinants responsible for observed subtype-specific replication differences.

Main Methods:

Keywords:
Gag-proteaseHIV-1 subtypeviral replication capacity

Related Experiment Videos

  • Patient-derived Gag-protease sequences were cloned into an HIV-1 NL4-3 backbone.
  • Recombinant virus replication capacities were quantified using flow cytometry in an HIV-1-inducible reporter T cell line.
  • Analyses were conducted using large, well-characterized cohorts from Africa and the Americas.

    • Main Results:

    • Gag-protease replication capacity significantly correlated with whole viral isolate replication capacity (r = 0.51, P = 0.04).
    • Subtype C Gag-proteases exhibited substantially lower replication capacities than subtype B Gag-proteases (P < 0.0001).
    • HIV-1 Gag residues 483 and 484, within the Alix-binding motif, were identified as key contributors to subtype-specific replication differences.
    • A hierarchy of Gag-protease-driven replication capacities was observed in East African cohorts: subtypes A/C < D < intersubtype recombinants (P < 0.0029).

    Conclusions:

    • HIV-1 Gag-protease is a major determinant of replication capacity and influences disease progression rates among different subtypes.
    • The lower Gag-protease-driven replication capacity of subtypes A and C may slow disease progression, potentially leading to increased transmission opportunities and prevalence.
    • Understanding these subtype-specific differences provides insights into HIV-1 epidemiology and informs strategies for disease control.