Mutations in the Protease Gene of Human Immunodeficiency Virus Type 1 Affect Release and Stability of Virus Particles

Virology ◽  
1993 ◽  
Vol 194 (2) ◽  
pp. 843-850 ◽  
Author(s):  
Jinseu Park ◽  
Casey D. Morrow
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Protease Gene ◽  
Virus Particles ◽  
Immunodeficiency Virus

scholarly journals Dissociation of Genome Dimerization from Packaging Functions and Virion Maturation of Human Immunodeficiency Virus Type 1

2002 ◽  
Vol 76 (3) ◽  
pp. 959-967 ◽  
Author(s):  
Jun-ichi Sakuragi ◽  
Aikichi Iwamoto ◽  
Tatsuo Shioda
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Viral Rna ◽  
Rna Packaging ◽  
Virus Particles ◽  
Immunodeficiency Virus ◽  
Rna Interaction ◽  
Hiv 1

ABSTRACT The dimer initiation site/dimer linkage sequence (DIS/DLS) region of the human immunodeficiency virus type 1 (HIV-1) RNA genome is thought to play important roles at various stages of the virus life cycle. Recently we showed that the DIS/DLS region affects RNA-RNA interaction in intact virus particles, by demonstrating that duplication of the region in viral RNA caused the production of virus particles containing partially monomeric RNAs. We have extended this finding and succeeded for the first time in creating mutant particles which contain only monomeric RNAs without modifying any viral proteins. In terms of RNA encapsidation ability, virion density, and protein processing, the mutant particles were comparable to wild-type particles. The level of production of viral DNA by the mutant virus construct in infected cells was also comparable to that of the constructs that produced exclusively dimeric RNA, indicating that monomeric viral RNA could be the template for strand transfer. These results indicated that the RNA dimerization of HIV-1 could be separated from viral RNA packaging and was not absolutely required for RNA packaging, virion maturation, and reverse transcription.

scholarly journals Human immunodeficiency virus type 1 Vpr: oligomerization is an essential feature for its incorporation into virus particles

2010 ◽  
Vol 7 (1) ◽  
pp. 119 ◽  
Author(s):  
Narasimhan J Venkatachari ◽  
Leah A Walker ◽  
Oznur Tastan ◽  
Thien Le ◽  
Timothy M Dempsey ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Essential Feature ◽  
Virus Particles ◽  
Immunodeficiency Virus

scholarly journals Human Immunodeficiency Virus Type 1 Nef Protein Is Incorporated into Virus Particles and Specifically Cleaved by the Viral Proteinase

Virology ◽  
1996 ◽  
Vol 219 (1) ◽  
pp. 228-236 ◽  
Author(s):  
REINHOLD WELKER ◽  
HUBERT KOTTLER ◽  
HANS ROBERT KALBITZER ◽  
HANS-GEORG KRÄUSSLICH
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Virus Particles ◽  
Immunodeficiency Virus

scholarly journals Selected amino acid substitutions in the C-terminal region of human immunodeficiency virus type 1 capsid protein affect virus assembly and release

2004 ◽  
Vol 85 (10) ◽  
pp. 2903-2913 ◽  
Author(s):  
Samir Abdurahman ◽  
Stefan Höglund ◽  
Laura Goobar-Larsson ◽  
Anders Vahlne
Keyword(s):  
Human Immunodeficiency Virus ◽  
Capsid Protein ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Infectious Clone ◽  
Particle Assembly ◽  
Virus Particles ◽  
Immunodeficiency Virus ◽  
Hiv 1

The capsid protein (CA or p24) of human immunodeficiency virus type 1 (HIV-1) plays a major role both early and late in the virus replication cycle. Many studies have suggested that the C-terminal domain of this protein is involved in dimerization and proper assembly of the viral core. Point mutations were introduced in two conserved sites of this region and their effects on viral protein expression, particle assembly and infectivity were studied. Eight different mutants (L205A+P207A, L205A, P207A, 223GPG225AAA, G223A, P224A, G225A and V221G) of the infectious clone pNL4-3 were constructed. Most substitutions had no substantial effect on HIV-1 protein synthesis, yet they impaired viral infectivity and particle production. The two mutants P207A and V221G also had a profound effect on Gag–Pol protein processing in HeLa–tat cells. However, these results were cell line-specific and Gag–Pol processing of P207A was not affected in 293T cells. In HeLa–tat cells, no virus particles were detected with the P207A mutation, whereas the other mutant virus particles were heterogeneous in size and morphology. None of the mutants showed normal, mature, conical core structures in HeLa–tat cells. These results indicate that the two conserved sequences in the C-terminal CA domain are essential for proper morphogenesis and infectivity of HIV-1 particles.

scholarly journals Fitness Landscape of Human Immunodeficiency Virus Type 1 Protease Quasispecies

2007 ◽  
Vol 81 (5) ◽  
pp. 2485-2496 ◽  
Author(s):  
Guerau Fernàndez ◽  
Bonaventura Clotet ◽  
Miguel Angel Martínez
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Fitness Landscape ◽  
Catalytic Efficiency ◽  
Viral Population ◽  
Protease Gene ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Here we show, at a high resolution (1%), the human immunodeficiency virus type 1 (HIV-1) protease gene quasispecies landscape from three infected naïve individuals. A huge range of genetic configurations was found (67%, 71%, and 80% of the nucleotide clones from the three individuals, respectively, were different), and these configurations created a dense net that linked different parts of the viral population. Similarly, a vast diversity of different protease activities was also found. Importantly, 65% of the analyzed enzymes had detectable protease activity, and 11% of the minority individual variants showed similar or better fitness than the master (most abundant) enzyme, suggesting that the viral complexity in this genomic region does not exclusively depend on the enzyme's catalytic efficiency. Several high-fitness minority variants had only one substitution compared to the master sequence, supporting the possibility that the rugged HIV-1 protease quasispecies fitness landscape may be formed by a continuous network that can be traversed by single mutational steps without passing through defective or less-adapted proteins.

scholarly journals Mutation of the Dominant Endocytosis Motif in Human Immunodeficiency Virus Type 1 gp41 Can Complement Matrix Mutations without Increasing Env Incorporation

2002 ◽  
Vol 76 (7) ◽  
pp. 3338-3349 ◽  
Author(s):  
John T. West ◽  
Sally K. Weldon ◽  
Stephanie Wyss ◽  
Xiaoxu Lin ◽  
Qin Yu ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Specific Interaction ◽  
Cytoplasmic Domain ◽  
Dependent Manner ◽  
Wild Type ◽  
Virus Particles ◽  
Immunodeficiency Virus

ABSTRACT The human immunodeficiency virus type 1 transmembrane glycoprotein (TM) is efficiently endocytosed in a clathrin-dependent manner. Internalization is mediated by a tyrosine-containing motif within the cytoplasmic domain, and replacement of the cytoplasmic tyrosine by cysteine or phenylalanine increased expression of mutant glycoprotein on the surface of transfected cells by as much as 2.5-fold. Because interactions between the cytoplasmic domain of Env and the matrix protein (MA) have been suggested to mediate incorporation of Env in virus particles, we examined whether perturbation of endocytosis would alter incorporation. Proviruses were constructed to contain the wild-type or mutant Env in conjunction with point mutations in MA that had previously been shown to block Env incorporation. These constructs were used to evaluate the effect of glycoprotein endocytosis on incorporation into virus particles and to test the necessity for a specific interaction between Env and MA to mediate incorporation. Viruses produced from transfected 293T cells were used to infect various cell lines, including MAGI, H9, and CEMx174. Viruses encoding both a disrupted endocytosis motif signal and mutations within MA were significantly more infectious in MAGI cells than their counterparts encoding a mutant MA and wild-type Env. This complementation of infectivity for the MA incorporation mutant viruses was not due to increased glycoprotein incorporation into particles but instead reflected an enhanced fusogenicity of the mutated Env proteins. Our findings further support the concept that a specific interaction between the long cytoplasmic domain of TM and MA is required for efficient incorporation of Env into assembling virions. Alteration of the endocytosis signal of Env, and the resulting increase in cell surface glycoprotein, has no effect on incorporation despite demonstrable effects on fusion, virus entry, and infectivity.

scholarly journals Selective Pressures of HLA Genotypes and Antiviral Therapy on Human Immunodeficiency Virus Type 1 Sequence Mutation at a Population Level

2007 ◽  
Vol 14 (10) ◽  
pp. 1266-1273 ◽  
Author(s):  
Golo Ahlenstiel ◽  
Kirsten Roomp ◽  
Martin Däumer ◽  
Jacob Nattermann ◽  
Martin Vogel ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Antiviral Drug ◽  
Protease Gene ◽  
Hla Genotypes ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The objective of this study was a comprehensive analysis of the immune-driven evolution of viruses of human immunodeficiency virus type 1 (HIV-1) clade B in a large patient cohort treated at a single hospital in Germany and its implications for antiretroviral therapy. We examined the association of the HLA-A, HLA-B, and HLA-DRB1 alleles with the emergence of mutations in the complete protease gene and the first 330 codons of the reverse transcriptase (RT) gene of HIV-1, studying their distribution and persistence and their impact on antiviral drug therapy. The clinical data for 179 HIV-infected patients, the results of HLA genotyping, and virus sequences were analyzed using a variety of statistical approaches. We describe new HLA-associated mutations in both viral protease and RT, several of which are associated with HLA-DRB1. The mutations reported are remarkably persistent within our cohort, developing more slowly in a minority of patients. Interestingly, several HLA-associated mutations occur at the same positions as drug resistance mutations in patient viruses, where the viral sequence was acquired before exposure to these drugs. The influence of HLA on thymidine analogue mutation pathways was not observed. We were able to confirm immune-driven selection pressure by major histocompatibility complex (MHC) class I and II alleles through the identification of HLA-associated mutations. HLA-B alleles were involved in more associations (68%) than either HLA-A (23%) or HLA-DRB1 (9%). As several of the HLA-associated mutations lie at positions associated with drug resistance, our results indicate possible negative effects of HLA genotypes on the development of HIV-1 drug resistance.

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