title: Alteration of the proline at position 7 of the HIV-1 spacer peptide p1 suppresses viral infectivity in a strain dependent manner.
abstract: The HIV-1 spacer peptide p1 is located in the C-terminus of the Gag polyprotein and separates the nucleocapsid (NC) and p6(Gag). 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-p6(Gag) C-terminus of HIV-1. We individually examined the role of p1 proline's in multiple strains of HIV-1 and investigated the role of three proline residues in p6(Gag) (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 p6(Gag). This work affords novel insights into our understanding of the role of p1 in HIV-1 replication.
authors.affiliation: Virology Program, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia. mel@burnet.edu.au
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Hill
authors.forename: Anna
authors.initials: A
authors.lastname: Bellamy-McIntyre
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Vella
authors.forename: Shahan M
authors.initials: SM
authors.lastname: Campbell
authors.forename: John A
authors.initials: JA
authors.lastname: Marshall
authors.forename: Gilda
authors.initials: G
authors.lastname: Tachedjian
authors.forename: Johnson
authors.initials: J
authors.lastname: Mak
mesh_terms: D000595:Amino Acid Sequence; D015683:Gene Products, gag / Q000737:chemistry* / Q000502:physiology; D015497:HIV-1 / Q000145:classification / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D011392:Proline / Q000737:chemistry*; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus
chemical_list: D015683:Gene Products, gag; D054301:gag Gene Products, Human Immunodeficiency Virus; C083868:gag protein p1, Human immunodeficiency virus; C083002:p6 gag protein, Human immunodeficiency virus 1; D011392:Proline