Frequent intrapatient recombination between human immunodeficiency virus type 1 R5 and X4 envelopes: implications for

Mattias Mild1, Joakim Esbjörnsson, Eva Maria Fenyö

  • 1Department of Experimental Medical Science, Lund University, BMC B13, 221 84 Lund, Sweden.

Journal of Virology
|January 26, 2007
PubMed

Insights

Intrapatient recombination between R5 and X4 human immunodeficiency virus type 1 (HIV-1) strains frequently creates CXCR4-using viruses. This viral evolution may contribute to disease progression and AIDS by evading immune responses and infecting CD4+ cells.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Human immunodeficiency virus type 1 (HIV-1) coreceptor usage switch from CCR5 (R5) to CXCR4 (X4) correlates with disease progression to AIDS.
  • Understanding the mechanisms driving this tropism switch is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying the coreceptor switch in HIV-1.
  • To determine the frequency and characteristics of viral recombination events contributing to CXCR4 usage.

Main Methods:

  • Sequencing of 253 V1 to V3 env clones from sequential HIV-1 subtype B isolates from four patients exhibiting coreceptor switching.
  • Experimental characterization of coreceptor usage for dualtropic R5X4 isolates.
  • Sequence analysis to identify recombination events.

Main Results:

  • Recombination between R5 and X4 viruses was identified as a frequent event (9% of clones from CXCR4-using isolates).
  • The majority (73%) of identified recombinants utilized CXCR4.
  • A small region of the viral envelope, including V3, was found to determine the coreceptor usage of these recombinants.

Conclusions:

  • Intrapatient recombination between HIV-1 strains with distinct coreceptor usage occurs frequently.
  • Chimeric viruses resulting from recombination can evade immune surveillance and infect CXCR4-expressing cells, potentially contributing to immune system impairment.
  • This recombination mechanism may play a significant role in the emergence of X4 viruses during later stages of HIV-1 infection.

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