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Table 1 Retrovirus mechanisms to modulate protein synthesis

From: Mechanisms employed by retroviruses to exploit host factors for translational control of a complicated proteome

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.
  1. a BLV, bovine leukemia virus; FeLV, feline leukemia virus; HFV, human foamy virus; HMSV, Harvey murine sarcoma 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; RSV, Rous sarcoma virus; SIV, simian immunodeficiency virus; SNV, spleen necrosis virus.