Table 1 Retrovirus mechanisms to modulate protein synthesis
Mechanism | Examples of viruses reported to utilize mechanisma | Effect on translation |
|---|---|---|
Internal Ribosome Entry Site (IRES) | HIV-1, HIV-2, SIV, HMSV, MLV, RSV | Cap-independent translation enhancer. Ribosomes plus a subset of initiation factors internally initiate translation independently of a 5' 7-methylguanosine cap. |
Post-transcriptional control element (PCE) | SNV, REV-A, HTLV-1, BLV, MPMV, FeLV, HIV-1, HFV | Novel 5' terminal cap-dependent translation enhancer. Specific interaction with RNA helicase A facilitates polysome loading and efficient viral protein production. PCE is not an IRES. |
Leaky scanning | HIV-1 | Readthrough of upstream AUG codons allows translation initiation of a downstream gene (i.e. vpu and env). |
Ribosome reinitiation | RSV | Short upstream open reading frames present in 5' leader RNA attenuate translation initiation at the authentic gag-pol AUG. Effect is dependent on distance from AUG. |
Frameshifting | Most retroviruses | Stimulatory signal and slippery sequence present in mRNA induce ribosome pausing and a -1 reading frame change. Results in translation of gag-pol open reading frame to produce reverse transcriptase and other enzymatic proteins. |
Termination codon readthrough | FeLV, MLV | Termination codon of gag open reading frame is read as glutamate. Results in translation of gag-pol open reading frame to produce reverse transcriptase and other enzymatic proteins. |
Ribosome shunt | Not determined | Scanning ribosome bypasses mRNA structural motif to reach AUG. |
Gag-gag mRNA interaction | RSV, HIV-1 | Gag protein binds to the 5' UTR of gag mRNA and attenuates translation efficiency. |
Cis -acting repressive sequences/inhibitory sequences (CRS/INS) | HIV-1 | AU-rich sequences present in gag, pol and env mRNA bind cellular proteins involved in mRNA metabolism and translation. This association represses cytoplasmic expression of the mRNA. |
Rev | HIV-1 | Viral regulatory protein recognizes intronic cis-acting Rev response element (RRE) and counteracts repression by INS/CRS. Trans-activates nuclear export, with coincide increases in mRNA stability and polysome loading that result in robust viral protein production. HTLV-1 Rex/RxRE and MMTV Rem/RmRE activity activate nuclear export and may likewise enhance translational output. |