Abstract
Besides viral proteins cellular factors play a key role in the replication of the human immunodeficiency virus HIV-1. The outcome of virus replication is determined by the balance between the activity of a number of cellular dependency factors and restriction factors. Whereas the first are essential cofactors for diverse steps in the viral replication cycle, the latter counteract virus replication by sensing particular viral components as non-self, often as mediators of the innate immune system. Cellular cofactors include receptors for HIV-1 entry, LEDGF as cofactor for the viral integrase, the RNA helicase DDX3 involved in the nuclear export of unspliced viral RNAs, and diverse cellular kinases that promote viral replication. Cellular restriction factors are often antagonized by HIV-1 accessory proteins in order to counteract their restrictive function on viral replication. Although cellular cofactors in the HIV field are understood as factors promoting viral replication, we add a subchapter on the most important restriction factors (Trim5α, APOBEC3G, SAMHD1, and tetherin/BST-2). Today highly active antiretroviral therapy (HAART) mostly targets HIV proteins like reverse transcriptase, protease, or integrase to specifically interfere with virus replication. However, the identification of cellular cofactors and the increasing knowledge on their mode of action at defined steps in the HIV-1 replication cycle have opened new avenues towards the development of HIV-1 inhibitors. Here we summarize the most important cellular factors involved in HIV-1 replication along with therapeutic approaches developed to target them, preferentially without harming their normal cellular function.
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Abbreviations
- β-TrCP:
-
β-transducin repeat containing protein
- APOBEC3G:
-
Apolipoprotein B mRNA editing enzyme 3G
- BRD4:
-
BET bromodomain protein 4
- BST-2:
-
Bone stromal protein 2
- CADA:
-
Cyclotriazadisulfonamide
- CCD:
-
Catalytic core domain
- CCR5:
-
Chemokine receptor 5
- CD4:
-
Cluster of differentiation 4
- CD4bs:
-
CD4 binding site
- CD4i:
-
CD4 induced
- CHR:
-
C-heptad repeat
- CRL:
-
Cullin ring E3 ligases
- CRM1:
-
Chromosome region maintenance 1
- CypA:
-
Cyclophylin A
- DCAF:
-
Ddb1-and Cul4 associated factor
- DC-SIGN:
-
Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin
- DDX3:
-
X-linked DEAD-box polypeptide 3
- DFS:
-
Dense fine speckles
- ECL:
-
Extracellular loop
- Env:
-
Envelope
- HAART:
-
Highly active antiretroviral therapy
- HDACI:
-
Histon deacetylase inhibitors
- HDGF:
-
Hepatoma-derived growth factor
- HCV:
-
Hepatitis C virus
- HCK:
-
Hematopoietic cell kinase
- HIV:
-
Human immunodeficiency virus
- HRP:
-
Hepatoma-derived growth factor-related proteins
- IBD:
-
Integrase binding domain
- IFN:
-
Interferon
- IN:
-
Integrase
- JAK1:
-
Janus kinase 1
- LEDGF:
-
Lens epithelium-derived growth factor
- mAb:
-
Monoclonal antibody
- MLL:
-
Mixed-lineage leukemia
- MPER:
-
Membrane proximal external region
- Nef:
-
Viral protein Nef (originally negative factor)
- NES:
-
Nuclear export signal
- NHR:
-
N-heptad repeat
- NLS:
-
Nuclear localization signal
- NV:
-
Norovirus
- PAMP:
-
Pathogen-associated molecular patterns
- PIC:
-
Preintegration complex
- PKC:
-
Protein kinase C
- P-TEFb:
-
Positive Transcription Elongation Factor b
- PSIP1:
-
PC4- and SFRS-interacting protein
- RIG:
-
RIG-like helicases
- RRE:
-
Rev responsive element
- sCD4:
-
Soluble CD4
- SAMHD1:
-
Sterile alpha motif (SAM) and Histidine/aspartate (HD) residues
- SDR:
-
Supercoiled DNA recognition domain
- Talens:
-
Transcription activator-like effector nucleases
- TLR:
-
Toll-like receptor
- TNPO3:
-
Transportin 3
- Trim5 α:
-
Tripartite motif 5α
- Vif:
-
Viral infectivity factor
- VIRIP:
-
Virus inhibitory peptide
- Vpr:
-
Viral protein R
- Vpx:
-
Viral protein X
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Dürr, R. et al. (2014). Targeting Cellular Cofactors in HIV Therapy. In: Diederich, W., Steuber, H. (eds) Therapy of Viral Infections. Topics in Medicinal Chemistry, vol 15. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7355_2014_45
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