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HIV-1 expression during early mammalian development.

K J Whitmer1, P G Calarco

  • 1Department of Biology, California State University, San Francisco 94143.

AIDS (London, England)
|October 1, 1992
PubMed
Summary
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This study demonstrates that the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) can be activated in early mouse embryo development before implantation. HIV-1 gene expression was observed as early as the eight-cell stage, offering insights into developmental pathologies.

Area of Science:

  • Developmental Biology
  • Molecular Virology
  • Genetics

Background:

  • Understanding human immunodeficiency virus type 1 (HIV-1) expression is crucial for developing therapeutic strategies and managing potential developmental risks.
  • The mouse model system provides a valuable platform for investigating the consequences of HIV-1 gene expression in mammalian embryonic development.

Purpose of the Study:

  • To determine the consequences of HIV-1 expression in the mammalian fetus using a mouse model.
  • To describe HIV gene expression during the pre-implantation period in micro-injected and electroporated mouse embryos.

Main Methods:

  • A non-infectious HIV system was created to assay HIV long terminal repeat (LTR) activation in mice.
  • Two constructs, RSV promoter-HIV tat gene and HIV LTR-lac Z gene, were co-micro-injected into fertilized mouse eggs or two-cell stage embryos.

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  • Electroporation and micro-injection techniques were compared for construct delivery efficiency and subsequent expression.

    • Main Results:

    • HIV-1 expression, indicated by beta-galactosidase production, was detected as early as the eight-cell to blastocyst stage in mouse embryos.
    • The intensity and proportion of embryonic cells expressing HIV varied significantly.
    • Integration of the constructs into the host genome could not be determined due to limited material.

    Conclusions:

    • The HIV-LTR can be activated during early mammalian development, prior to embryonic implantation.
    • The observed HIV-1 expression rate in early development was low, averaging slightly over 1%.
    • These findings are significant for research on HIV-transgenic mice, factors influencing HIV expression, and potential developmental pathologies associated with HIV.