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

doi:10.1006/viro.2001.1300

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 journal › Article › peer-review

18 Scopus citations

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 language	English
Pages (from-to)	1-12
Number of pages	12
Journal	Virology
Volume	294
Issue number	1
DOIs	https://doi.org/10.1006/viro.2001.1300
State	Published - 2002
Externally published	Yes

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

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.",

author = "Malgorzata Simm and Miller, {Lloyd S.} and Durkin, {Helen G.} and Melrose Allen and Wei Chao and Adam Lesner and Potash, {Mary Jane} and Volsky, {David J.}",

note = "Funding Information: We thank Dr. G. Bentsman for excellent technical assistance, Dr. C. Rosen for pSVTat, Dr. J. Hoxie who provided antibody 12G-5 through the AIDS Research and Reference Reagent Repository, Dr. G. McKinley who provided blood samples from AIDS patients, and Ms. I. Totillo for manuscript preparation. This work was supported by Grant 02685-28-RGV from the American Foundation for AIDS Research (M.S.), and PHS Grants AI44344 (M.S.), AI43913 (D.J.V.), and NS39191 (M.J.P.).",

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T1 - Induction of secreted human immunodeficiency virus type 1 (HIV-1) resistance factors in CD4-positive T lymphocytes by attenuated HIV-1 infection

AU - Simm, Malgorzata

AU - Miller, Lloyd S.

AU - Durkin, Helen G.

AU - Allen, Melrose

AU - Chao, Wei

AU - Lesner, Adam

AU - Potash, Mary Jane

AU - Volsky, David J.

N1 - Funding Information: We thank Dr. G. Bentsman for excellent technical assistance, Dr. C. Rosen for pSVTat, Dr. J. Hoxie who provided antibody 12G-5 through the AIDS Research and Reference Reagent Repository, Dr. G. McKinley who provided blood samples from AIDS patients, and Ms. I. Totillo for manuscript preparation. This work was supported by Grant 02685-28-RGV from the American Foundation for AIDS Research (M.S.), and PHS Grants AI44344 (M.S.), AI43913 (D.J.V.), and NS39191 (M.J.P.).

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

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

Abstract

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