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Related Experiment Videos

Envelope sequence variation, neutralizing antibodies, and primate lentivirus persistence

D P Burns1, R C Desrosiers

  • 1New England Regional Primate Research Center, Harvard Medical School, Southborough, MA 01772-9102.

Current Topics in Microbiology and Immunology
|January 1, 1994
PubMed
Summary

During chronic lentivirus infection, neutralization-resistant variants emerge due to immune selection. Host antibodies drive sequence changes in viral envelopes, leading to escape mutants that limit replication.

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Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Chronic lentivirus infections, including ungulate lentiviruses and simian immunodeficiency virus (SIV), are characterized by the emergence of viral variants over time.
  • Previous studies suggested the immune system, particularly humoral immunity, acts as a selective force, but lacked molecularly cloned viruses for definitive proof.

Purpose of the Study:

  • To provide definitive evidence that neutralization-resistant variants emerge during persistent primate lentivirus infection.
  • To investigate the evolution of viral envelope sequences and the emergence of neutralization resistance in SIV-infected rhesus monkeys.

Main Methods:

  • Cloning viral envelope genes from rhesus monkeys over time and collecting sequential serum samples.
  • Performing reciprocal neutralization studies using parental and variant-specific sera.

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  • Utilizing molecularly cloned virus of defined sequence to demonstrate immune selection.

    • Main Results:

    • Persistent infection with SIV and HIV exerts selective pressure for changes in discrete variable regions of the viral envelope.
    • The host's neutralizing antibody response is a key selective force, driving sequence variation and the emergence of neutralization escape mutants.
    • Neutralization domains of HIV and SIV correlate with variable regions (V1-V6), suggesting a direct link between antibody targets and sequence evolution.

    Conclusions:

    • Neutralizing antibodies play a crucial role in limiting lentivirus replication during the asymptomatic phase of infection.
    • Sequence variation in viral envelopes, particularly in variable regions, is driven by host immune responses, leading to the emergence of escape variants.
    • While antibodies are a major selective force, other factors like tropism and T-cell responses may also contribute to sequence changes in specific viral domains.