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Related Experiment Videos

Functional complementation of the envelope hypervariable V3 loop of human immunodeficiency virus type 1 subtype B by

H Sato1, K Kato, Y Takebe

  • 1Laboratory of Molecular Virology and Epidemiology, AIDS Research Center, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku, Tokyo, 162-8640, Japan. hirosato@nih.go.jp

Virology
|May 18, 1999
PubMed
Summary

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The V3 loop of subtype E human immunodeficiency virus type 1 (HIV-1) dictates viral tropism and coreceptor usage. This finding is crucial for understanding HIV-1 evolution and developing targeted therapies.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • The V3 loop of HIV-1 gp120 is a key determinant of viral tropism and coreceptor usage.
  • Limited data exists on V3 loop function in non-subtype B HIV-1 strains, particularly subtype E prevalent in Southeast Asia.

Purpose of the Study:

  • To investigate the functional role of the HIV-1 subtype E V3 loop in determining cell tropism, coreceptor preference, and chemokine sensitivity.
  • To understand the structure-function relationship of the V3 loop in subtype E.

Main Methods:

  • Construction of HIV-1LAI recombinants with subtype E V3 loops (NSI and SI variants) using overlap extension.
  • Infection assays using peripheral blood mononuclear cells, MT2 cells, and HOS-CD4(+) cells.
  • Assessment of coreceptor usage (CXCR4, CCR5) and CC-chemokine sensitivity.

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Main Results:

  • All recombinant viruses infected peripheral blood mononuclear cells.
  • Syncytium-inducing (SI) V3 recombinants infected MT2 cells, while non-syncytium-inducing (NSI) V3 recombinants did not.
  • SI V3 recombinants utilized CXCR4, whereas NSI V3 recombinants utilized CCR5 for infection.
  • The NSI V3 sequence conferred CC-chemokine sensitivity to the parental virus.

Conclusions:

  • The HIV-1 V3 loop functions as an independent domain within gp120.
  • The subtype E V3 loop contains the essential elements for dictating viral cell tropism, coreceptor preference, and chemokine sensitivity.
  • These findings are vital for understanding HIV-1 V3 structure-function and the evolution of subtype E.