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A whole genome screen for HIV restriction factors
- Source :
- Retrovirology, Vol 8, Iss 1, p 94 (2011), Retrovirology
- Publication Year :
- 2011
- Publisher :
- BMC, 2011.
-
Abstract
- Background Upon cellular entry retroviruses must avoid innate restriction factors produced by the host cell. For human immunodeficiency virus (HIV) human restriction factors, APOBEC3 (apolipoprotein-B-mRNA-editing-enzyme), p21 and tetherin are well characterised. Results To identify intrinsic resistance factors to HIV-1 replication we screened 19,121 human genes and identified 114 factors with significant inhibition of infection. Those with a known function are involved in a broad spectrum of cellular processes including receptor signalling, vesicle trafficking, transcription, apoptosis, cross-nuclear membrane transport, meiosis, DNA damage repair, ubiquitination and RNA processing. We focused on the PAF1 complex which has been previously implicated in gene transcription, cell cycle control and mRNA surveillance. Knockdown of all members of the PAF1 family of proteins enhanced HIV-1 reverse transcription and integration of provirus. Over-expression of PAF1 in host cells renders them refractory to HIV-1. Simian Immunodeficiency Viruses and HIV-2 are also restricted in PAF1 expressing cells. PAF1 is expressed in primary monocytes, macrophages and T-lymphocytes and we demonstrate strong activity in MonoMac1, a monocyte cell line. Conclusions We propose that the PAF1c establishes an anti-viral state to prevent infection by incoming retroviruses. This previously unrecognised mechanism of restriction could have implications for invasion of cells by any pathogen.
- Subjects :
- lcsh:Immunologic diseases. Allergy
HIV Infections
Biology
Virus Replication
Cell Line
03 medical and health sciences
Transcription (biology)
Virology
Humans
Transcription factor
030304 developmental biology
0303 health sciences
Gene knockdown
Genome, Human
Research
030302 biochemistry & molecular biology
HIV
Nuclear Proteins
Proteins
Provirus
Reverse transcriptase
mRNA surveillance
3. Good health
Infectious Diseases
Viral replication
Host-Pathogen Interactions
Commentary
Tetherin
Interferon
Therapy
Host restriction factors
lcsh:RC581-607
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 17424690
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Retrovirology
- Accession number :
- edsair.doi.dedup.....2a35fd45b53ed1e60b3b8b301ff5daa2