Induction of secreted human immunodeficiency virus type 1 (HIV-1) resistance factors in CD4-positive T lymphocytes by attenuated HIV-1 infection

Malgorzata Simm, Lloyd S. Miller, Helen G. Durkin, Melrose Allen, Wei Chao, Adam Lesner, Mary Jane Potash, David J. Volsky

Research output: Contribution to journalArticlepeer-review

Abstract

This report describes induction of HIV-1 resistance and synthesis of resistance factors in immortal CD4-positive T lymphocytes. SupT1 cells were infected by NL4-3 attenuated by a defect in the vif gene through coculture with infected primary lymphocytes. Cell lines from this infection, termed R1, expressed CD4 and CXCR4, carried low levels of HIV-1 DNA, but expressed no other detectable viral products and were resistant to infection by wild-type HIV-1. Investigation of challenge infection in resistant R1 lines demonstrated entry, reverse transcription, and integration by incoming HIV-1 but no synthesis of viral RNA. By assay of marker gene expression, we found that Tat was unable to activate LTR-driven transcription in R1 lines. HIV-1-resistant R1 lines secreted soluble factors that inhibited productive infection of primary lymphocytes by several strains of HIV-1 and blocked viral RNA synthesis in newly infected cells. Resistance factors also blocked the induction of HIV-1 transcription in ACH-2 cells as assayed by viral antigen expression and Northern blot of viral RNA. Soluble factors produced by HIV-1-resistant, immortal R1 cells may form the basis of new approaches to control HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalVirology
Volume294
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Virology

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