Table 2.
Retrovirus:host interactions involved in retroviral translation control
Host factor | Examples of interacting virusa | Effect on translation | |
Interacts with retrovirus protein & RNA | Protein kinase R (PKR) | HIV-1, HTLV-1 | HIV-1 Tat reduces PKR autophosphorylation. Tat and eIF2α compete as substrates of PKR. High levels of HIV-1 TAR RNA or HTLV-1 RxRE inhibit PKR autophosphorylation. |
Small RNA pathway components (Dicer & Drosha) |
PFV, HIV-1 | PFV Tas and HIV-1 Tat act as RNA silencing suppressors that combat the antiviral effect of small RNA pathway. Also miRNAs may be encoded by retroviruses that downregulate host antiviral defense. | |
Interacts with retrovirus RNA | TAR RNA binding protein (TRBP) | HIV-1 | Binding of TRBP to HIV-1 TAR RNA results in increased HIV-1 transcription and translation. |
2', 5'-oligoadenylate-synthetase/RNaseL | HIV-1, HTLV-1 | HIV-1 5' UTR RNA binds 2-5OAS resulting in RNAseL activity in vitro. HIV-1 infection is associated with reduced interferon production and reduced 2-5A:RNAseL binding, allowing HIV-1 mRNA to evade cleavage by RNaseL. HTLV-1 RxRE activates 2-5OAS in vitro. | |
RNA helicase A (RHA or DHX9) |
SNV, REV-A, HTLV-1, MPMV, HFV, FeLV, BLV, HIV-1 | RHA binds PCE mRNA leading to increased polysome association and efficient protein synthesis. | |
9G8 | MPMV | In overexpression experiments, hyper-phosphorylated 9G8 binds constitutive transport element-containing reporter mRNA resulting in increased polysome accumulation and protein synthesis. | |
Sam68, SLM-1, SLM-2 | HIV-1, HTLV-1, EIAV, MPMV | Sam68, SLM-1 and SLM-2 act synergistically with HIV-1 Rev, HTLV-1 Rex and EIAV ERev to facilitate expression and proper cytoplasmic localization of RRE-containing mRNA. Sam68 also enhances translation of mRNA containing the MPMV constitutive transport element. | |
hnRNP E1 | HIV-1 | hnRNPE1 binds HIV-1 mRNA at the exon splicing silencer in Rev exon (ESSE) and reduces Gag, Env, and Rev protein production. | |
eRF1 | MLV | MLV reverse transcriptase binds eRF1 promoting readthrough of the gag termination codon to produce proteins encoded by gag-pol. |
a BLV, bovine leukemia virus; EIAV, equine infectious anemia virus; FeLV, feline leukemia virus; HFV, human foamy virus; HTLV-1, human T-cell leukemia virus type 1; MLV, murine leukemia virus; MPMV, Mason-Pfizer monkey virus; REV-A, reticuloendotheliosis virus strain A; SNV, spleen necrosis virus.