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A human cell factor is essential for HIV-1 Rev action.

D Trono1, D Baltimore

  • 1Whitehead Institute for Biomedical Research, Cambridge, MA 02142.

The EMBO Journal
|December 1, 1990
PubMed
Summary

Murine cells can initiate HIV replication but fail due to a defective Rev protein. Complementing with human cells restores HIV growth, revealing a cellular factor critical for Rev function and HIV tropism.

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Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Human Immunodeficiency Virus (HIV) replication is complex, involving multiple viral and cellular factors.
  • Understanding HIV tropism, the range of cells it can infect, is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the permissiveness of murine cells to HIV infection.
  • To identify the specific stage of the HIV life cycle restricted in murine cells.

Main Methods:

  • NIH 3T3 murine cells were infected with HIV pseudotyped by Moloney murine leukemia virus.
  • Rev function was assessed by analyzing the expression of incompletely spliced HIV mRNAs.
  • Complementary assays were performed by fusing infected murine cells with uninfected human cells.

Main Results:

  • Murine cells supported early HIV replication steps including uncoating, reverse transcription, nuclear transport, and integration.
  • Several murine cell lines and CHO cells failed to support the function of the viral regulatory gene, Rev.
  • The Rev defect was not rescued by HTLV-1 rex, but was complemented by fusion with human cells.

Conclusions:

  • Murine cells are permissive to early HIV replication but restrict later stages due to a defect in Rev function.
  • A trans-acting cellular factor, critical for Rev function, is absent or non-functional in murine cells.
  • This cellular factor contributes to the determination of HIV tropism.

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