Genetic drift and within-host metapopulation dynamics of HIV-1 infection

S D Frost1, M J Dumaurier, S Wain-Hobson

  • 1Department of Pathology, University of California, San Diego, CA 92103, USA. sdfrost@ucsd.edu

Insights

This study introduces a metapopulation model for HIV replication, revealing that founder effects and turnover in small cell subpopulations significantly impact viral genetic diversity. This challenges existing models by highlighting genetic drift

Area of Science:

  • Virology
  • Immunology
  • Population Genetics

Background:

  • HIV replication primarily occurs in lymphoid tissues with distinct histological structures.
  • Current HIV population models often assume random mixing (panmixis) within these tissues.
  • This assumption may oversimplify the complex dynamics of viral evolution in vivo.

Purpose of the Study:

  • To propose and test a metapopulation model for HIV replication that accounts for localized infection dynamics.
  • To investigate the role of founder effects and subpopulation turnover in shaping viral genetic variation.
  • To understand how these factors influence the effective population size and genetic drift of HIV.

Main Methods:

  • Development of a simple metapopulation model for HIV replication.
  • Analysis of viral genetic variation within infected cell subpopulations in the spleen.
  • Comparison of genetic differentiation between subpopulations across different patients.

Main Results:

  • Demonstration of founder effects in spleen-derived infected cell subpopulations.
  • Significant inter-patient variability in the degree of genetic differentiation between subpopulations.
  • Evidence that founder effects and turnover reduce the effective population size of HIV.

Conclusions:

  • The metapopulation model provides a more realistic framework for understanding HIV replication dynamics.
  • Founder effects and subpopulation turnover are crucial factors in HIV evolution within lymphoid tissues.
  • These localized processes contribute to the significance of genetic drift in HIV, despite a large overall number of infected cells.

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