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

Retrovirology

Michael H Malim³  Stuart JD Neil³  Kevin Olivieri¹  Baek Kim²  Sarah M Amie²  Rui Pedro Galão³  Torsten Schaller³  Caroline Goujon³ 

[1] Infectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute, La Jolla, USA;Department of Microbiology and Immunology, University of Rochester Medical, Rochester, USA;Department of Infectious Diseases, King’s College London, 2nd Floor, Borough Wing, Guy’s Hospital, London Bridge, London SE1 9RT, UK

关键词: Deoxyribonucleosides;    Vpx;    SAMHD1;    Macrophages;    Restriction;    Interferon;    HIV-1;   

Others  :  1209157
DOI  :  10.1186/1742-4690-10-23

 received in 2012-11-26, accepted in 2013-02-19,  发布年份 2013

【 摘 要 】

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 IFNα-inducible. Myeloid cell infection by HIV-1 is enhanced by HIV-2/SIV_SM Vpx, which promotes SAMHD1 degradation, or by exogenous deoxyribonucleoside (dN) addition.

Findings

SAMHD1 expression was not substantially influenced by IFNα treatment of monocyte-derived macrophages or THP-1 cells. The contributions of SAMHD1 to the inhibition of HIV-1 infectivity by IFNα 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 IFNα-treated macrophages, albeit not to the levels seen with these treatments in the absence of IFNα. 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 IFNα. Neither Vpx addition nor SAMHD1 knock-down reversed the IFNα-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 IFNα-induced restriction to HIV-1 infection seen in many cells and cell lines.

Conclusion

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

【 授权许可】

   
2013 Goujon et al; licensee BioMed Central Ltd.

【 图 表 】

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