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The capsid-spacer peptide 1 Gag processing intermediate is a dominant-negative inhibitor of HIV-1 maturation

Checkley, Mary Ann ; Luttge, Benjamin G ; Soheilian, Ferri ; Nagashima, Kunio ; Freed, Eric O

Virology (New York, N.Y.), 2010-04, Vol.400 (1), p.137-144 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
The capsid-spacer peptide 1 Gag processing intermediate is a dominant-negative inhibitor of HIV-1 maturation
Autor: Checkley, Mary Ann ; Luttge, Benjamin G ; Soheilian, Ferri ; Nagashima, Kunio ; Freed, Eric O
Assuntos: Amino Acid Sequence ; Anti-HIV Agents - pharmacology ; Assembly ; Capsid Proteins - genetics ; Capsid Proteins - physiology ; Cell Line ; Gag ; gag Gene Products, Human Immunodeficiency Virus - genetics ; gag Gene Products, Human Immunodeficiency Virus - physiology ; HeLa Cells ; HIV-1 ; HIV-1 - drug effects ; HIV-1 - genetics ; HIV-1 - physiology ; Human immunodeficiency virus 1 ; Humans ; Infectious Disease ; Jurkat Cells ; Molecular Sequence Data ; Mutation ; Protease ; Protein Processing, Post-Translational ; Retrovirus ; Succinates - pharmacology ; Triterpenes - pharmacology ; Virus Assembly ; Virus maturation ; Virus Replication - drug effects
É parte de: Virology (New York, N.Y.), 2010-04, Vol.400 (1), p.137-144
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Descrição: Abstract The human immunodeficiency virus type 1 (HIV-1) maturation inhibitor bevirimat disrupts virus replication by inhibiting the cleavage of the capsid-spacer peptide 1 (CA-SP1) Gag processing intermediate to mature CA. The observation that bevirimat delays but does not completely block CA-SP1 processing suggests that the presence of uncleaved CA-SP1 may disrupt the maturation process in trans . In this study, we validate this hypothesis by using a genetic approach to demonstrate that a non-cleavable CA-SP1 mutant exerts a dominant-negative effect on maturation of wild-type HIV-1. In contrast, a mutant in which cleavage can occur internally within SP1 is significantly less potent as a dominant-negative inhibitor. We also show that bevirimat blocks processing at both the major CA-SP1 cleavage site and the internal site. These data underscore the importance of full CA-SP1 processing for HIV-1 maturation and highlight the therapeutic potential of inhibitors that target this Gag cleavage event.
Editor: United States: Elsevier Inc
Idioma: Inglês

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The capsid-spacer peptide 1 Gag processing intermediate is a dominant-negative inhibitor of HIV-1 maturation

Checkley, Mary Ann ; Luttge, Benjamin G ; Soheilian, Ferri ; Nagashima, Kunio ; Freed, Eric O

United States: Elsevier Inc

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