HIV expression strategies: Ribosomal frameshifting is directed by a short sequence in both mammalian and yeast systems

Wilson, Wilma; Braddock, Martin; Adams, Sally E.; Rathjen, Peter D.; Kingsman, Susan M.; Kingsman, Alan J.

doi:10.1016/0092-8674(88)90260-7

Cited by 205 publications

(176 citation statements)

References 33 publications

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“…The absence of HIV-like particle production seemed to be due to modification of the amino-terminal portion of the gag protein which is essential for particle formation (8). Failure in synthesizing RT suggested that the ribosomal frameshift in mRNA translation (14,46) was very inefficient in this case for unknown reasons.…”

Section: Resultsmentioning

confidence: 99%

Immune Response of Mice Infected with Recombinant Vaccinia Viruses Carrying the HIV gag Gene

Sugata

Aoki

Shioda

et al. 1991

Microbiology and Immunology

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We examined mouse immune response to 4 kinds of recombinant vaccinia viruses carrying the HIV gag gene, including vac-gag/pol, which produces HIV-like particles with processed gag proteins; vac-gag, which also produces HIV-like particles but with unprocessed gag protein; and vac-gag-pol-fuse and vac-es-gag/pol, neither of which produces such particles but releases reverse transcriptase and gag protein, respectively, from infected cells. Although infection of mice with recombinant vaccinia viruses induced production of the anti-p24 antibody in all mice, vac-gag/pol and vac-es-pol induced higher production than the other two recombinants. Increase in [3H]thymidine uptake by splenic lymphocytes following p24 antigen stimulation was most evident in mice infected with vac-gag/pol. Thus, the highest immune reaction, both humoral and cellular, was elicited by vac-gag/pol, indicating that among those tested, this recombinant vaccinia virus is the best candidate for a vaccine that induces anti-HIV gag immunity.

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Section: Resultsmentioning

confidence: 99%

Immune Response of Mice Infected with Recombinant Vaccinia Viruses Carrying the HIV gag Gene

Sugata

Aoki

Shioda

et al. 1991

Microbiology and Immunology

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“…To rule out this possibility, we examined whether inhibition of eRF1 activity enhances PRF in another system. We chose to utilize the yeast S. cerevisiae as a model system for further testing because it has been reported that the HIV-1 PRF signal could direct frameshifting in this system (10). A yeast strain was employed in which the endogenous eRF1 allele was inactivated and replaced with a plasmid expressing a temperature-sensitive mutant of the eRF1 gene (I222S) (38) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The rules governing PRF appear to be universal in eukaryotes because it has been shown that the PRF signals from mammalian viruses function in yeast cells (8,10,31).…”

mentioning

confidence: 99%

Identification of a Cellular Factor That Modulates HIV-1 Programmed Ribosomal Frameshifting

Kobayashi¹,

Zhuang²,

Peltz

et al. 2010

Journal of Biological Chemistry

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Programmed ؊1 ribosomal frameshifting (PRF) is a distinctive mode of gene expression utilized by some viruses, including human immunodeficiency virus type 1 (HIV-1), to produce multiple proteins from a single mRNA. ؊1 PRF induces a subset of elongating ribosomes to shift their translational reading frame by 1 base in the 5 direction. The appropriate ratio of Gag to Gag-Pol synthesis is tightly regulated by the PRF signal which promotes ribosomes to shift frame, and even small changes in PRF efficiency, either up or down, have significant inhibitory effects upon virus production, making PRF essential for HIV-1 replication. Although little has been reported about the cellular factors that modulate HIV-1 PRF, the cis-acting elements regulating PRF have been extensively investigated, and the PRF signal of HIV-1 was shown to include a slippery site and frameshift stimulatory signal. Recently, a genome-wide screen performed to identify cellular factors that affect HIV-1 replication demonstrated that down-regulation of eukaryotic release factor 1 (eRF1) inhibited HIV-1 replication. Because of the eRF1 role in translation, we hypothesized that eRF1 is important for HIV-1 PRF. Using a dual luciferase reporter system harboring a HIV-1 PRF signal, results showed that depletion or inhibition of eRF1 enhanced PRF in yeast, rabbit reticulocyte lysates, and mammalian cells. Consistent with the eRF1 role in modulating HIV PRF, depleting eRF1 increased the Gag-Pol to Gag ratio in cells infected with replication-competent virus. The increase in PRF was independent of a proximal termination codon and did not result from increased ribosomal pausing at the slippery site. This is the first time that a cellular factor has been identified which can promote HIV-1 PRF and highlights HIV-1 PRF as essential for replication and an important but under exploited antiviral drug target.The ability of ribosomes to maintain the correct translational open reading frame (ORF) 2 is fundamental to the integrity and fidelity of protein synthesis. However, there are a number of examples in which elongating ribosomes are programmed to shift their translational ORF 1 base in either the 5Ј or 3Ј direction (Ϫ1 or ϩ1 ribosomal programmed ribosomal frameshift (PRF), respectively) to translate multiple proteins from a single mRNA (1-5). HIV-1 is one example of a virus that uses this process as an integral part of its replication cycle.The HIV-1 Gag and Pol proteins are synthesized as p55 Gag or p160Gag-Pol polyprotein precursors using the same translation start codon but different ORFs in the full-length viral mRNA (6, 7). The gag ORF is located at the 5Ј end of the viral mRNA, whereas the pol ORF is 3Ј of the HIV-1 PRF element and outof-frame with the gag ORF (Fig. 1). Therefore, the enzymatic protein products of the pol gene are only translated through a Ϫ1 PRF event (8 -10). Importantly, the frequency of the PRF is controlled precisely via the interaction between viral RNA cisacting elements and host translation factors. The frequency of the PRF in HIV-1...

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“…This event leads the translation to proceed past the normal stop codon using another reading frame, resulting in a polyprotein precursor Prl60gag-pol (Figs. 1, 2) [11,12]. This larger polyprotein comprises the amino acids of Pr55gag up to residue 432 in the nuclear capsid protein part p7, which are fused to the sequences synthesized from the "poP' gene of the HIV genome (pol = open reading frame encoding virus protease, reverse transcriptase and integrase).…”

Section: Formation Of Infectious Hiv Particles: a Multistep Proceduresmentioning

confidence: 99%

The gag proteins of human immunodeficiency virus type 1: mechanisms of virus assembly and possibilities for interference

Modrow

Kattenbeck

Poblotzki

et al. 1994

Med Microbiol Immunol

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HIV expression strategies: Ribosomal frameshifting is directed by a short sequence in both mammalian and yeast systems

Cited by 205 publications

References 33 publications

Immune Response of Mice Infected with Recombinant Vaccinia Viruses Carrying the HIV gag Gene

Immune Response of Mice Infected with Recombinant Vaccinia Viruses Carrying the HIV gag Gene

Identification of a Cellular Factor That Modulates HIV-1 Programmed Ribosomal Frameshifting

The gag proteins of human immunodeficiency virus type 1: mechanisms of virus assembly and possibilities for interference

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