Abstract
The HIV-1 spacer peptide p1 is located in the C-terminus of the Gag polyprotein and separates the nucleocapsid (NC) and p6Gag. Research centered on p1 has been limited and as yet no function has been ascribed to this spacer peptide. We have previously found that the conserved p1 proline residues (position 7 and 13) are critical for replication in the HIV-1 strain HXB2-BH10. In this study we have focused on the proline rich p1-p6Gag C-terminus of HIV-1. We individually examined the role of p1 prolines in multiple strains of HIV-1 and investigated the role of three proline residues in p6Gag (P24, P25 and P30). Assessment of the HXB2-BH10 based mutants revealed that Gag-Pol incorporation relative to Gag decreased in the p1 mutant virions, with the double proline mutant the most impaired. Mutating both p1 proline residues was found to abolish infectivity in multiple strains of HIV-1. Independent mutation of the p1 proline at position 7 resulted in a strain-dependent suppression of viral infectivity. This defect correlates with the presence of a tyrosine residue at position 9 of p1 and occurs in the early phase of the HIV-1 replication cycle. The p1 proline residues were found to be functionally distinct from P24, P25 and P30 in p6Gag. This work affords novel insights into our understanding of the role of p1 in HIV-1 replication.
Keywords: HIV, spacer peptide, p1, p6Gag, Gag
Current HIV Research
Title: Alteration of the Proline at Position 7 of the HIV-1 Spacer Peptide p1 Suppresses Viral Infectivity in a Strain Dependent Manner
Volume: 5 Issue: 1
Author(s): Melissa K. Hill, Anna Bellamy-McIntyre, Laura J. Vella, Shahan M. Campbell, John A. Marshall, Gilda Tachedjian and Johnson Mak
Affiliation:
Keywords: HIV, spacer peptide, p1, p6Gag, Gag
Abstract: The HIV-1 spacer peptide p1 is located in the C-terminus of the Gag polyprotein and separates the nucleocapsid (NC) and p6Gag. Research centered on p1 has been limited and as yet no function has been ascribed to this spacer peptide. We have previously found that the conserved p1 proline residues (position 7 and 13) are critical for replication in the HIV-1 strain HXB2-BH10. In this study we have focused on the proline rich p1-p6Gag C-terminus of HIV-1. We individually examined the role of p1 prolines in multiple strains of HIV-1 and investigated the role of three proline residues in p6Gag (P24, P25 and P30). Assessment of the HXB2-BH10 based mutants revealed that Gag-Pol incorporation relative to Gag decreased in the p1 mutant virions, with the double proline mutant the most impaired. Mutating both p1 proline residues was found to abolish infectivity in multiple strains of HIV-1. Independent mutation of the p1 proline at position 7 resulted in a strain-dependent suppression of viral infectivity. This defect correlates with the presence of a tyrosine residue at position 9 of p1 and occurs in the early phase of the HIV-1 replication cycle. The p1 proline residues were found to be functionally distinct from P24, P25 and P30 in p6Gag. This work affords novel insights into our understanding of the role of p1 in HIV-1 replication.
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Cite this article as:
Hill K. Melissa, Bellamy-McIntyre Anna, Vella J. Laura, Campbell M. Shahan, Marshall A. John, Tachedjian Gilda and Mak Johnson, Alteration of the Proline at Position 7 of the HIV-1 Spacer Peptide p1 Suppresses Viral Infectivity in a Strain Dependent Manner, Current HIV Research 2007; 5 (1) . https://dx.doi.org/10.2174/157016207779316323
DOI https://dx.doi.org/10.2174/157016207779316323 |
Print ISSN 1570-162X |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4251 |
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