Myristoylation of<i>gag</i>Proteins of HIV-1 Plays an Important Role in Virus Assembly

Pal, Ranajit; Reitz, Marvin S.; Tschachler, Erwin; Gallo, Rosella; Sarngadharan, M. G.; Veronese, Fulvia

doi:10.1089/aid.1990.6.721

Cited by 106 publications

(102 citation statements)

References 14 publications

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“…None of the single or double mutation constructs showed reduction of VLP production, indicating that these single or double mutations were not sufficient for determining the amino acids responsible for VLP production in the D1 region. All arenavirus Z and several retroviral Gag proteins have been reported to be myristoylated at G2 for attachment to the cellular membrane (Bryant & Ratner, 1990;Göttlinger et al, 1989;Pal et al, 1990;Urata & Yasuda, 2012;Urata et al, 2009), and this attachment is critical for the assembly and production of infectious progeny virions. To produce Lassa VLP, the aa 3-10 sequence does not have to be specific for LASV Z, as substitution of this region with HIV-1 Gag and RSV v-src recovered the defect of D1 VLP production, although the degree of recovery did not completely reach the WT level (Fig.…”

Section: Discussionmentioning

confidence: 99%

Cis- and cell-type-dependent trans-requirements for Lassa virus-like particle production

Urata

Yasuda

2015

Journal of General Virology

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Lassa virus (LASV) small zinc-finger protein (Z), which contains two L-domain motifs, plays a central role in virus budding. Here, we report that co-expression of glycoprotein (GPC) altered the requirements for cholesterol but not the L-domains and host factor, Tsg101, for Z-induced viruslike particle (VLP) production. In particular, the cholesterol requirement for VLP production was cell-type-dependent. In addition, GPC was found to be important for co-localization of Z with CD63, a late endosomal marker. We also found that the N-terminal region (aa 3-10) of Z was critical for its myristoylation and VLP production. These findings will contribute to our understanding of LASV assembly and budding.

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Section: Discussionmentioning

confidence: 99%

Cis- and cell-type-dependent trans-requirements for Lassa virus-like particle production

Urata

Yasuda

2015

Journal of General Virology

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“…Gag and abolishes viral budding (5,22,38), providing a negative control for viral replication. To ensure that no other mutations had spontaneously occurred in the cloning process, SIVmac239 mutants were verified by sequencing the entire coding region of the viral genome.…”

Section: Alignment Of Lentiviral Pr55mentioning

confidence: 99%

Hydrogen Bonding at a Conserved Threonine in Lentivirus Capsid Is Required for Virus Replication

Rue

Roos

Amzel

et al. 2003

J Virol

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The N terminus of the capsid protein (CA) undergoes a considerable conformational change when the human immunodeficiency virus (HIV) protease cleaves it free from the Pr55Gag polyprotein. This rearrangement is thought to facilitate the establishment of specific CA-CA interactions that are required for the formation of the mature viral core. Substitution of amino acids that are critical for this refolding of the N terminus is generally detrimental to virus replication and mature virion core morphology. Here, we identify a conserved threonine in simian immunodeficiency virus (SIV) CA, T ( As hydrogen bonding between these two residues is present in HIV CA as well, this interaction presents a potential target for antiviral drug design.

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“…Gag is crucial for the binding of Gag to membrane and is thus required for virus assembly (4,18,23,51). A highly basic region spanning MA residues 17 to 31 has also been implicated in Gag membrane binding.…”

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confidence: 99%

Role of the Gag Matrix Domain in Targeting Human Immunodeficiency Virus Type 1 Assembly

Ono

Orenstein

Freed

2000

J Virol

220

236

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Human immunodeficiency virus type 1 (HIV-1) particle formation and the subsequent initiation of proteasemediated maturation occur predominantly on the plasma membrane. However, the mechanism by which HIV-1 assembly is targeted specifically to the plasma membrane versus intracellular membranes is largely unknown. Previously, we observed that mutations between residues 84 and 88 of the matrix (MA) domain of HIV-1 Gag cause a retargeting of virus particle formation to an intracellular site. In this study, we demonstrate that the mutant virus assembly occurs in the Golgi or in post-Golgi vesicles. These particles undergo core condensation in a protease-dependent manner, indicating that virus maturation can occur not only on the plasma membrane but also in the Golgi or post-Golgi vesicles. The intracellular assembly of mutant particles is dependent on Gag myristylation but is not influenced by p6Gag or envelope glycoprotein expression. Previous characterization of viral revertants suggested a functional relationship between the highly basic domain of MA (amino acids 17 to 31) and residues 84 to 88. We now demonstrate that mutations in the highly basic domain also retarget virus particle formation to the Golgi or post-Golgi vesicles. Although the basic domain has been implicated in Gag membrane binding, no correlation was observed between the impact of mutations on membrane binding and Gag targeting, indicating that these two functions of MA are genetically separable. Plasma membrane targeting of Gag proteins with mutations in either the basic domain or between residues 84 and 88 was rescued by coexpression with wild-type Gag; however, the two groups of MA mutants could not rescue each other. We propose that the highly basic domain of MA contains a major determinant of HIV-1 Gag plasma membrane targeting and that mutations between residues 84 and 88 disrupt plasma membrane targeting through an effect on the basic domain.

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Myristoylation ofgagProteins of HIV-1 Plays an Important Role in Virus Assembly

Cited by 106 publications

References 14 publications

Cis- and cell-type-dependent trans-requirements for Lassa virus-like particle production

Cis- and cell-type-dependent trans-requirements for Lassa virus-like particle production

Hydrogen Bonding at a Conserved Threonine in Lentivirus Capsid Is Required for Virus Replication

Role of the Gag Matrix Domain in Targeting Human Immunodeficiency Virus Type 1 Assembly

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