Evidence for IFNalpha-induced, SAMHD1-independent inhibitors of early HIV-1 infection

Caroline Goujon; Torsten Schaller; Rui Pedro Galao Ribeiro Galao; Sarah M. Amie; Baek Kim; Kevin Olivieri; Stuart J. D. Neil; Michael H. Malim

doi:10.1186/1742-4690-10-23

Evidence for IFNalpha-induced, SAMHD1-independent inhibitors of early HIV-1 infection

Caroline Goujon, Torsten Schaller, Rui Pedro Galao Ribeiro Galao, Sarah M. Amie, Baek Kim, Kevin Olivieri, Stuart J. D. Neil, Michael H. Malim^*

^*Corresponding author for this work

Infectious Diseases

Research output: Contribution to journal › Article › peer-review

53 Citations (Scopus)

Abstract

Background: Type I interferon (IFN) treatment of some cells, including dendritic cells, macrophages and monocytic THP-1 cells, restricts HIV-1 infection and prevents viral cDNA accumulation. Sterile alpha motif and HD domain protein 1 (SAMHD1), a dGTP-regulated deoxynucleotide triphosphohydrolase, reduces HIV-1 infectivity in myeloid cells, likely by limiting dNTPs available for reverse transcription, and has been described as IFN alpha-inducible. Myeloid cell infection by HIV-1 is enhanced by HIV-2/SIVSM Vpx, which promotes SAMHD1 degradation, or by exogenous deoxyribonucleoside (dN) addition.

Findings: SAMHD1 expression was not substantially influenced by IFN alpha treatment of monocyte-derived macrophages or THP-1 cells. The contributions of SAMHD1 to the inhibition of HIV-1 infectivity by IFN alpha were assessed through the provision of Vpx, exogenous dN addition, or via RNAi-mediated SAMHD1 knock-down. Both Vpx and dN efficiently restored infection in IFN alpha-treated macrophages, albeit not to the levels seen with these treatments in the absence of IFN alpha. Similarly using differentiated THP-1 cells, the addition of Vpx or dNs, or SAMHD1 knock-down, also stimulated infection, but failing to match the levels observed without IFN alpha. Neither Vpx addition nor SAMHD1 knock-down reversed the IFN alpha-induced blocks to HIV-1 infection seen in dividing U87-MG or THP-1 cells. Therefore, altered SAMHD1 expression or function cannot account for the IFN alpha induced restriction to HIV-1 infection seen in many cells and cell lines.

Conclusion: IFN alpha establishes an anti-HIV-1 phenotype in many cell types, and appears to accomplish this without potentiating SAMHD1 function. We conclude that additional IFN alpha-induced suppressors of the early stages of HIV-1 infection await identification.

Original language	English
Article number	23
Pages (from-to)	N/A
Number of pages	6
Journal	Retrovirology
Volume	10
Issue number	N/A
DOIs	https://doi.org/10.1186/1742-4690-10-23
Publication status	Published - 25 Feb 2013

Keywords

HIV-1
Interferon
Restriction
Macrophages
SAMHD1
Vpx
Deoxyribonucleosides
PRIMARY HUMAN MACROPHAGES
HUMAN DENDRITIC CELLS
CD4(+) T-CELLS
INTERFERON
VPX
RESTRICTION
TRANSDUCTION
PROTEINS
GAMMA

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/1742-4690-10-23

Cite this

@article{b98272306b014f7ea689eb80db4ff973,

title = "Evidence for IFNalpha-induced, SAMHD1-independent inhibitors of early HIV-1 infection",

abstract = "Background: Type I interferon (IFN) treatment of some cells, including dendritic cells, macrophages and monocytic THP-1 cells, restricts HIV-1 infection and prevents viral cDNA accumulation. Sterile alpha motif and HD domain protein 1 (SAMHD1), a dGTP-regulated deoxynucleotide triphosphohydrolase, reduces HIV-1 infectivity in myeloid cells, likely by limiting dNTPs available for reverse transcription, and has been described as IFN alpha-inducible. Myeloid cell infection by HIV-1 is enhanced by HIV-2/SIVSM Vpx, which promotes SAMHD1 degradation, or by exogenous deoxyribonucleoside (dN) addition.Findings: SAMHD1 expression was not substantially influenced by IFN alpha treatment of monocyte-derived macrophages or THP-1 cells. The contributions of SAMHD1 to the inhibition of HIV-1 infectivity by IFN alpha were assessed through the provision of Vpx, exogenous dN addition, or via RNAi-mediated SAMHD1 knock-down. Both Vpx and dN efficiently restored infection in IFN alpha-treated macrophages, albeit not to the levels seen with these treatments in the absence of IFN alpha. Similarly using differentiated THP-1 cells, the addition of Vpx or dNs, or SAMHD1 knock-down, also stimulated infection, but failing to match the levels observed without IFN alpha. Neither Vpx addition nor SAMHD1 knock-down reversed the IFN alpha-induced blocks to HIV-1 infection seen in dividing U87-MG or THP-1 cells. Therefore, altered SAMHD1 expression or function cannot account for the IFN alpha induced restriction to HIV-1 infection seen in many cells and cell lines.Conclusion: IFN alpha establishes an anti-HIV-1 phenotype in many cell types, and appears to accomplish this without potentiating SAMHD1 function. We conclude that additional IFN alpha-induced suppressors of the early stages of HIV-1 infection await identification.",

keywords = "HIV-1, Interferon, Restriction, Macrophages, SAMHD1, Vpx, Deoxyribonucleosides, PRIMARY HUMAN MACROPHAGES, HUMAN DENDRITIC CELLS, CD4(+) T-CELLS, INTERFERON, VPX, RESTRICTION, TRANSDUCTION, PROTEINS, GAMMA",

author = "Caroline Goujon and Torsten Schaller and {Ribeiro Galao}, {Rui Pedro Galao} and Amie, {Sarah M.} and Baek Kim and Kevin Olivieri and Neil, {Stuart J. D.} and Malim, {Michael H.}",

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doi = "10.1186/1742-4690-10-23",

language = "English",

volume = "10",

pages = "N/A",

journal = "Retrovirology",

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T1 - Evidence for IFNalpha-induced, SAMHD1-independent inhibitors of early HIV-1 infection

AU - Goujon, Caroline

AU - Schaller, Torsten

AU - Ribeiro Galao, Rui Pedro Galao

AU - Amie, Sarah M.

AU - Kim, Baek

AU - Olivieri, Kevin

AU - Neil, Stuart J. D.

AU - Malim, Michael H.

PY - 2013/2/25

Y1 - 2013/2/25

N2 - Background: Type I interferon (IFN) treatment of some cells, including dendritic cells, macrophages and monocytic THP-1 cells, restricts HIV-1 infection and prevents viral cDNA accumulation. Sterile alpha motif and HD domain protein 1 (SAMHD1), a dGTP-regulated deoxynucleotide triphosphohydrolase, reduces HIV-1 infectivity in myeloid cells, likely by limiting dNTPs available for reverse transcription, and has been described as IFN alpha-inducible. Myeloid cell infection by HIV-1 is enhanced by HIV-2/SIVSM Vpx, which promotes SAMHD1 degradation, or by exogenous deoxyribonucleoside (dN) addition.Findings: SAMHD1 expression was not substantially influenced by IFN alpha treatment of monocyte-derived macrophages or THP-1 cells. The contributions of SAMHD1 to the inhibition of HIV-1 infectivity by IFN alpha were assessed through the provision of Vpx, exogenous dN addition, or via RNAi-mediated SAMHD1 knock-down. Both Vpx and dN efficiently restored infection in IFN alpha-treated macrophages, albeit not to the levels seen with these treatments in the absence of IFN alpha. Similarly using differentiated THP-1 cells, the addition of Vpx or dNs, or SAMHD1 knock-down, also stimulated infection, but failing to match the levels observed without IFN alpha. Neither Vpx addition nor SAMHD1 knock-down reversed the IFN alpha-induced blocks to HIV-1 infection seen in dividing U87-MG or THP-1 cells. Therefore, altered SAMHD1 expression or function cannot account for the IFN alpha induced restriction to HIV-1 infection seen in many cells and cell lines.Conclusion: IFN alpha establishes an anti-HIV-1 phenotype in many cell types, and appears to accomplish this without potentiating SAMHD1 function. We conclude that additional IFN alpha-induced suppressors of the early stages of HIV-1 infection await identification.

AB - Background: Type I interferon (IFN) treatment of some cells, including dendritic cells, macrophages and monocytic THP-1 cells, restricts HIV-1 infection and prevents viral cDNA accumulation. Sterile alpha motif and HD domain protein 1 (SAMHD1), a dGTP-regulated deoxynucleotide triphosphohydrolase, reduces HIV-1 infectivity in myeloid cells, likely by limiting dNTPs available for reverse transcription, and has been described as IFN alpha-inducible. Myeloid cell infection by HIV-1 is enhanced by HIV-2/SIVSM Vpx, which promotes SAMHD1 degradation, or by exogenous deoxyribonucleoside (dN) addition.Findings: SAMHD1 expression was not substantially influenced by IFN alpha treatment of monocyte-derived macrophages or THP-1 cells. The contributions of SAMHD1 to the inhibition of HIV-1 infectivity by IFN alpha were assessed through the provision of Vpx, exogenous dN addition, or via RNAi-mediated SAMHD1 knock-down. Both Vpx and dN efficiently restored infection in IFN alpha-treated macrophages, albeit not to the levels seen with these treatments in the absence of IFN alpha. Similarly using differentiated THP-1 cells, the addition of Vpx or dNs, or SAMHD1 knock-down, also stimulated infection, but failing to match the levels observed without IFN alpha. Neither Vpx addition nor SAMHD1 knock-down reversed the IFN alpha-induced blocks to HIV-1 infection seen in dividing U87-MG or THP-1 cells. Therefore, altered SAMHD1 expression or function cannot account for the IFN alpha induced restriction to HIV-1 infection seen in many cells and cell lines.Conclusion: IFN alpha establishes an anti-HIV-1 phenotype in many cell types, and appears to accomplish this without potentiating SAMHD1 function. We conclude that additional IFN alpha-induced suppressors of the early stages of HIV-1 infection await identification.

KW - HIV-1

KW - Interferon

KW - Restriction

KW - Macrophages

KW - SAMHD1

KW - Vpx

KW - Deoxyribonucleosides

KW - PRIMARY HUMAN MACROPHAGES

KW - HUMAN DENDRITIC CELLS

KW - CD4(+) T-CELLS

KW - INTERFERON

KW - VPX

KW - RESTRICTION

KW - TRANSDUCTION

KW - PROTEINS

KW - GAMMA

U2 - 10.1186/1742-4690-10-23

DO - 10.1186/1742-4690-10-23

M3 - Article

C2 - 23442224

SN - 1742-4690

VL - 10

SP - N/A

JO - Retrovirology

JF - Retrovirology

IS - N/A

M1 - 23

ER -

Evidence for IFNalpha-induced, SAMHD1-independent inhibitors of early HIV-1 infection

Abstract

Keywords

UN SDGs

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