Assembly and Release of Human Immunodeficiency Virus Type 1 Gag Proteins Containing Tandem Repeats of the Matrix Protein Coding Sequences in the Matrix Domain

Wang, Chin Tien; Chen, Steve S.-L.; Chiang, Chien Cheng

doi:10.1006/viro.2000.0655

Cited by 5 publications

(3 citation statements)

References 48 publications

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“…Previous reports have demonstrated that while the globular head of HIV-1 MA can exert a negative effect on virus assembly in some cellular contexts (Hatziioannou et al, 2005;Hubner and Chen, 2006;Perez-Caballero et al, 2004), large sequence insertions into MA can be accommodated for the purposes of VLP assembly and release (Liao et al, 2004;Muller et al, 2004;Wang et al, 2000). Moreover, matrix domain swapping studies have revealed that some chimeric retrovirus PrGag proteins efficiently assemble virions that can be infectious (Chen et al, 2001;Reed et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Analysis of human immunodeficiency virus matrix domain replacements

et al. 2008

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The matrix (MA) domain of the HIV-1 structural precursor Gag (PrGag) protein targets PrGag proteins to membrane assembly sites, and facilitates incorporation of envelope proteins into virions. To evaluate the specific requirements for the MA membrane-binding domain (MBD) in HIV-1 assembly and replication, we examined viruses in which MA was replaced by alternative MBDs. Results demonstrated that the pleckstrin homology domains of AKT protein kinase and phospholipase C delta1 efficiently directed the assembly and release of virus-like particles (VLPs) from cells expressing chimeric proteins. VLP assembly and release also were mediated in a phorbol ester-dependent fashion by the cysteine-rich binding domain of phosphokinase Cgamma. Although alternative MBDs promoted VLP assembly and release, the viruses were not infectious. Notably, PrGag processing was reduced, while cleavage of GagPol precursors resulted in the accumulation of Pol-derived intermediates within virions. Our results indicate that the HIV-1 assembly machinery is flexible with regard to its means of membrane association, but that alternative MBDs can interfere with the elaboration of infectious virus cores.

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Section: Discussionmentioning

confidence: 99%

Analysis of human immunodeficiency virus matrix domain replacements

et al. 2008

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“…It may be possible to design a chimeric Gag protein that is directed to the plasma membrane in mouse cells by the MLV MA, but at the same time retains MA sequences responsible for HIV-1 Env incorporation. HIV-1 clones engineered to carry tandem copies of HIV-1 MA are still capable of efficient HIV-1 assembly (39). Thus, it may be possible to make a chimeric Gag that keeps the HIV-1 MA and tags the HIV-1 Gag at the N terminus with MLV MA or MA-p12.…”

Section: Discussionmentioning

confidence: 99%

Efficient assembly of an HIV-1/MLV Gag-chimeric virus in murine cells

Chen

Rousso

Shim

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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In human cells infected by HIV type 1 (HIV-1), the viral Gag protein directs the assembly of nascent viral particles at the plasma membrane. In murine cells, HIV-1 Gag fails to reach the plasma membrane and instead forms nonfunctional intracellular aggregates. The viral determinants of this species incompatibility are previously undefined. To address this problem, we replaced a region of HIV-1 Gag known to direct its localization, the matrix (MA) domain, with functionally homologous regions from Moloney murine leukemia virus (MLV), a murine retrovirus. An HIV-1 clone carrying such a chimeric Gag protein, designated murine HIV (MHIV), assembled more efficiently than nonchimeric HIV-1 and restored plasma membrane localization of Gag in murine cells. Increased efficiency of viral assembly in murine cells was observed from MHIV constructs carrying MLV MA in place of HIV-1 MA. Efficient processing of the HIV-1 capsid protein from the chimeric Gag polyprotein and subsequent infectivity of MHIV required the presence of MLV p12 in addition to MLV MA. These findings strongly suggest that the HIV-1 MA domain of HIV-1 Gag is responsible for the assembly defect in mouse cells. Although these MHIV do not recruit native HIV-1 Env efficiently, they are capable of single-round infection when produced by high-efficiency transfection of human 293 cells and provided with an HIV-1 Env lacking its cytoplasmic tail. With further adaptation, this chimeric MHIV approach may provide the basis for creating an infectious mouse model for HIV/AIDS.

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“…Because the db5 mutation with a deletion of the basic domain may affect the Gag membrane binding, and because it was found previously that the insertion of the duplicated 107-MA codons in HIV matrix region could enhance Gag membrane affinity [Wang et al, 2000a], the effect of db5 mutation was tested on Gag membrane binding in the presence or absence of the duplicated matrix-coding sequence by equilibrium flotation centrifugation experiments. To exclude possible effects of Gag processing on the estimation of the amounts of membrane-associated Gag precursors, the wt and mutants were expressed in a protease-defective (PR À ) version.…”

Section: Differential Effects Of the Db5 Mutation On Gagmentioning

confidence: 99%

Effects of mutations in an HIV‐1 gag gene containing a 107‐codon tandem repeat in the matrix region on assembly and processing of the protein product

Liao

Chiu

Wang

2004

Journal of Medical Virology

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It has been demonstrated previously that a human immunodeficiency virus (HIV) type 1 Gag mutant (MA2) with a tandem repeat of 107-matrix codons in the matrix domain could direct virus particle assembly and budding [Wang et al. (2000c): J Med Virol 61:423-432]. Since the regions involved functionally in HIV Gag assembly and transport have been mapped to the matrix domain, it was interesting to test the effects of the duplicated matrix-coding sequence on Gag assembly, transport, and virus processing of some assembly-defective HIV matrix mutants. In this study, a number of HIV matrix mutations were introduced into either the proximal or distal copy of the duplicated matrix-coding sequence. Assembly, release, processing, and subcellular localization of the Gag mutants were analyzed by transient expression in 293T cells. The result indicates that the budding defect of HIV matrix mutants could be moderately or significantly reversed when the additional 107-matrix codons were present; however, these matrix double mutations affected significantly the virus particle processing. Mislocalized matrix mutants could also be redistributed to a certain degree in the presence of the duplicated matrix copy. Although the subcellular distribution patterns of the matrix mutants did not correlate completely with the budding efficiency, the data suggest that the budding defect caused by the matrix mutations could be masked to some extent by the duplicated matrix coding sequence.

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Assembly and Release of Human Immunodeficiency Virus Type 1 Gag Proteins Containing Tandem Repeats of the Matrix Protein Coding Sequences in the Matrix Domain

Cited by 5 publications

References 48 publications

Analysis of human immunodeficiency virus matrix domain replacements

Analysis of human immunodeficiency virus matrix domain replacements

Efficient assembly of an HIV-1/MLV Gag-chimeric virus in murine cells

Effects of mutations in an HIV‐1 gag gene containing a 107‐codon tandem repeat in the matrix region on assembly and processing of the protein product

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