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HIV-1 protease with leucine zipper fused at N-terminus exhibits enhanced linker amino acid-dependent activity

Overview of attention for article published in Retrovirology, April 2018
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Title
HIV-1 protease with leucine zipper fused at N-terminus exhibits enhanced linker amino acid-dependent activity
Published in
Retrovirology, April 2018
DOI 10.1186/s12977-018-0413-6
Pubmed ID
Authors

Fu-Hsien Yu, Chin-Tien Wang

Abstract

HIV-1 protease (PR) activation is triggered by Gag-Pol dimerization. Premature PR activation results in reduced virion yields due to enhanced Gag cleavage. A p6* transframe peptide located directly upstream of protease is believed to play a modulating role in PR activation. Previous reports indicate that the C-terminal p6* tetra-peptide prevents premature PR activation triggered by a leucine zipper (LZ) dimerization motif inserted in the deleted p6* region. To clarify the involvement of C-terminal p6* residues in mitigating enhanced LZ-incurred Gag processing, we engineered constructs containing C-terminal p6* residue substitutions with and without a mutation blocking the p6*/PR cleavage site, and created other Gag or p6* domain-removing constructs. The capabilities of these constructs to mediate virus maturation were assessed by Western blotting and single-cycle infection assays. p6*-PR cleavage blocking did not significantly reduce the LZ enhancement effect on Gag cleavage when only four amino acid residues were present between the p6* and PR. This suggests that the potent LZ dimerization motif may enhance PR activation by facilitating PR dimer formation, and that PR precursors may trigger sufficient enzymatic activity without breaking off from the PR N-terminus. Enhanced LZ-induced activation of PR embedded in Gag-Pol was found to be independent of the Gag assembly domain. In contrast, the LZ enhancement effect was markedly reduced when six amino acids were present at the p6*-PR junction, in part due to impaired PR maturation by substitution mutations. We also observed that a proline substitution at the P3 position eliminated the ability of p6*-deleted Gag-Pol to mediate virus maturation, thus emphasizing the importance of C-terminal p6* residues to modulating PR activation. The ability of HIV-1 C-terminal p6* amino acid residues to modulate PR activation contributes, at least in part, to their ability to counteract enhanced Gag cleavage induced by a leucine zipper substituted for a deleted p6*. Changes in C-terminal p6* residues between LZ and PR may affect PR-mediated virus maturation, thus providing a possible method for assessing HIV-1 protease precursor activation in the context of virus assembly.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 2 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 2 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 1 50%
Student > Master 1 50%
Readers by discipline Count As %
Immunology and Microbiology 1 50%
Unknown 1 50%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 April 2018.
All research outputs
#8,039,090
of 12,818,993 outputs
Outputs from Retrovirology
#514
of 781 outputs
Outputs of similar age
#161,420
of 271,280 outputs
Outputs of similar age from Retrovirology
#1
of 1 outputs
Altmetric has tracked 12,818,993 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 781 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 23rd percentile – i.e., 23% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 271,280 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them