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Role of the Gag matrix domain in targeting human immunodeficiency virus type 1 assembly.
J Virol. 2000 Mar; 74(6):2855-66.JV

Abstract

Human immunodeficiency virus type 1 (HIV-1) particle formation and the subsequent initiation of protease-mediated 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 p6(Gag) 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.

Authors+Show Affiliations

Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0460, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10684302

Citation

Ono, A, et al. "Role of the Gag Matrix Domain in Targeting Human Immunodeficiency Virus Type 1 Assembly." Journal of Virology, vol. 74, no. 6, 2000, pp. 2855-66.
Ono A, Orenstein JM, Freed EO. Role of the Gag matrix domain in targeting human immunodeficiency virus type 1 assembly. J Virol. 2000;74(6):2855-66.
Ono, A., Orenstein, J. M., & Freed, E. O. (2000). Role of the Gag matrix domain in targeting human immunodeficiency virus type 1 assembly. Journal of Virology, 74(6), 2855-66.
Ono A, Orenstein JM, Freed EO. Role of the Gag Matrix Domain in Targeting Human Immunodeficiency Virus Type 1 Assembly. J Virol. 2000;74(6):2855-66. PubMed PMID: 10684302.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of the Gag matrix domain in targeting human immunodeficiency virus type 1 assembly. AU - Ono,A, AU - Orenstein,J M, AU - Freed,E O, PY - 2000/2/23/pubmed PY - 2000/2/23/medline PY - 2000/2/23/entrez SP - 2855 EP - 66 JF - Journal of virology JO - J. Virol. VL - 74 IS - 6 N2 - Human immunodeficiency virus type 1 (HIV-1) particle formation and the subsequent initiation of protease-mediated 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 p6(Gag) 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. SN - 0022-538X UR - https://www.unboundmedicine.com/medline/citation/10684302/Role_of_the_Gag_matrix_domain_in_targeting_human_immunodeficiency_virus_type_1_assembly_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=10684302 DB - PRIME DP - Unbound Medicine ER -