scholarly journals P3 An insertion of seven amino acids in the envelope cytoplasmic tail of human immunodeficiency virus type 2 (HIV-2) selected during disease progression enhances viral replication

2017 ◽  
Vol 3 ◽  
pp. 4
Author(s):  
FrançoisE Dufrasne ◽  
Mara Lucchetti ◽  
Anandi Martin ◽  
Jean Ruelle ◽  
Patrick Goubau
Keyword(s):  
Amino Acids ◽  
Human Immunodeficiency Virus ◽  
Viral Replication ◽  
Disease Progression ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cytoplasmic Tail ◽  
Immunodeficiency Virus

scholarly journals Cellular Membrane-Binding Ability of the C-Terminal Cytoplasmic Domain of Human Immunodeficiency Virus Type 1 Envelope Transmembrane Protein gp41

2001 ◽  
Vol 75 (20) ◽  
pp. 9925-9938 ◽  
Author(s):  
Steve S.-L. Chen ◽  
Sheau-Fen Lee ◽  
Chin-Tien Wang
Keyword(s):  
Amino Acids ◽  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Membrane Binding ◽  
Cytoplasmic Tail ◽  
Cellular Membrane ◽  
C Terminus ◽  
Immunodeficiency Virus

ABSTRACT The amphipathic α-helices located in the cytoplasmic tail of the envelope (Env) transmembrane glycoprotein gp41 of human immunodeficiency virus type 1 have been implicated in membrane association and cytopathicity. Deletion of the last 12 amino acids in the C terminus of this domain severely impairs infectivity. However, the nature of the involvement of the cytoplasmic tail in Env-membrane interactions in cells and the molecular basis for the defect in infectivity of this mutant virus are still poorly understood. In this study we examined the interaction of the cytoplasmic tail with membranes in living mammalian cells by expressing a recombinant cytoplasmic tail fragment and an Escherichia coli β-galactosidase/cytoplasmic tail fusion protein, both of them lacking gp120, the gp41 ectodomain, and the transmembrane region. We found through cell fractionation, in vivo membrane flotation, and confocal immunofluorescence studies that the cytoplasmic tail contained determinants to be routed to a perinuclear membrane region in cells. Further mapping showed that each of the three lentivirus lytic peptide (LLP-1, LLP-2, and LLP-3) sequences conferred this cellular membrane-targeting ability. Deletion of the last 12 amino acids from the C terminus abolished the ability of the LLP-1 motif to bind to membranes. High salt extraction, in vitro transcription and translation, and posttranslational membrane binding analyses indicated that the β-galactosidase/LLP fusion proteins were inserted into membranes via the LLP sequences. Subcellular fractionation and confocal microscopy studies revealed that each of the LLP motifs, acting in a position-independent manner, targeted non-endoplasmic reticulum (ER)-associated β-galactosidase and enhanced green fluorescence protein to the ER. Our study provides a basis for the involvement of the gp41 cytoplasmic tail during Env maturation and also supports the notion that the membrane apposition of the C-terminal cytoplasmic tail plays a crucial role in virus-host interaction.

scholarly journals Lack of Effect of Cytoplasmic Tail Truncations on Human Immunodeficiency Virus Type 2 ROD Env Particle Release Activity

1999 ◽  
Vol 73 (1) ◽  
pp. 778-782 ◽  
Author(s):  
Stephan P. Bour ◽  
Claudia Aberham ◽  
Christèle Perrin ◽  
Klaus Strebel
Keyword(s):  
Human Immunodeficiency Virus ◽  
Biological Activity ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Amino Acid Level ◽  
Cytoplasmic Tail ◽  
Site Directed Mutagenesis ◽  
Particle Release ◽  
Immunodeficiency Virus

ABSTRACT In addition to its role in receptor binding, the envelope glycoprotein of certain human immunodeficiency virus type 2 (HIV-2) isolates, including ROD10, exhibits a biological activity that enhances the release of HIV-2, HIV-1, and simian immunodeficiency virus particles from infected cells. The present study aims at better defining the functional domains involved in this biological activity. To this end, we have characterized the envelope protein of the ROD14 isolate of HIV-2, which, despite 95% homology with the ROD10 envelope at the amino acid level, is unable to enhance viral particle release. Site-directed mutagenesis showed that the presence of a truncation in the cytoplasmic tail of the ROD14 envelope was not responsible for the lack of activity, as previously reported for the HIV-2 ST isolate (G. D. Ritter, Jr., G. Yamshchikov, S. J. Cohen, and M. J. Mulligan, J. Virol. 70:2669–2673, 1996). Similarly, several modifications of the length of the ROD10 envelope cytoplasmic tail did not impair its ability to enhance particle release, suggesting that, in the case of the HIV-2 ROD isolate, particle release activity is not regulated by the length of the cytoplasmic tail.

scholarly journals Mutational Analysis of Conserved Domains within the Cytoplasmic Tail of gp41 from Human Immunodeficiency Virus Type 1: Effects on Glycoprotein Incorporation and Infectivity

2000 ◽  
Vol 74 (24) ◽  
pp. 11717-11723 ◽  
Author(s):  
Sabine C. Piller ◽  
John W. Dubay ◽  
Cynthia A. Derdeyn ◽  
Eric Hunter
Keyword(s):  
Amino Acids ◽  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cytoplasmic Tail ◽  
Progeny Virus ◽  
Multiple Infection ◽  
Immunodeficiency Virus

ABSTRACT The transmembrane (TM) glycoprotein gp41 of human immunodeficiency virus type 1 possesses an unusually long (∼150 amino acids) and highly conserved cytoplasmic region. Previous studies in which this cytoplasmic tail had been deleted partially or entirely have suggested that it is important for virus infectivity and incorporation of the gp120-gp41 glycoprotein complex into virions. To determine which regions of the conserved C-terminal domains are important for glycoprotein incorporation and infectivity, several small deletions and amino acid substitutions which modify highly conserved motifs were constructed in the infectious proviral background of NL4.3. The effects of these mutations on infectivity and glycoprotein incorporation into virions produced from transfected 293-T cells and infected H9 and CEM×174 cells were determined. With the exception of a mutation deleting amino acids QGL, all of the constructs resulted in decreased infectivity of the progeny virus both in a single-round infectivity assay and in a multiple-infection assay in H9 and CEM×174 cells. For most mutations, the decreased infectivity was correlated with a decreased incorporation of glycoprotein into virions. Substitution of the arginines (residues 839 and 846) with glutamates also reduced infectivity, but without a noticeable decrease in the amount of glycoprotein incorporated into virus produced from infected T cells. These results demonstrate that minor alterations in the conserved C-terminal region of the gp41 cytoplasmic tail can result in reductions in infectivity that correlate for most but not all constructs with a decrease in glycoprotein incorporation. Observed cell-dependent differences suggest the involvement of cellular factors in regulating glycoprotein incorporation and infectivity.

scholarly journals Modulation of Different Human Immunodeficiency Virus Type 1 Nef Functions during Progression to AIDS

2001 ◽  
Vol 75 (8) ◽  
pp. 3657-3665 ◽  
Author(s):  
Silke Carl ◽  
Thomas C. Greenough ◽  
Mandy Krumbiegel ◽  
Michael Greenberg ◽  
Jacek Skowronski ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Replication ◽  
Disease Progression ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Independent Functions ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) Nef protein has several independent functions that might contribute to efficient viral replication in vivo. Since HIV-1 adapts rapidly to its host environment, we investigated if different Nef properties are associated with disease progression. Functional analysis revealed thatnef alleles obtained during late stages of infection did not efficiently downmodulate class I major histocompatibility complex but were highly active in the stimulation of viral replication. In comparison, functional activity in downregulation of CD4 and enhancement of HIV-1 infectivity were maintained or enhanced after AIDS progression. Our results demonstrate that various Nef activities are modulated during the course of HIV-1 infection to maintain high viral loads at different stages of disease progression. These findings suggest that all in vitro Nef functions investigated contribute to AIDS pathogenesis and indicate that nef variants with increased pathogenicity emerge in a significant number of HIV-1-infected individuals.

Dispensable role of the human immunodeficiency virus type 2 Vpx protein in viral replication.

1991 ◽  
Vol 65 (7) ◽  
pp. 3938-3942 ◽  
Author(s):  
L Marcon ◽  
F Michaels ◽  
N Hattori ◽  
K Fargnoli ◽  
R C Gallo ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Replication ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus

scholarly journals Human immunodeficiency virus type 1 gp120 envelope characteristics associated with disease progression differ in family members infected with genetically similar viruses

2013 ◽  
Vol 94 (1) ◽  
pp. 20-29 ◽  
Author(s):  
Elly Baan ◽  
Renée M. van der Sluis ◽  
Margreet E. Bakker ◽  
Vincent Bekker ◽  
Dasja Pajkrt ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Disease Progression ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Positive Charge ◽  
Gp120 Envelope ◽  
Immunodeficiency Virus ◽  
Virus Strains ◽  
Hiv 1

The human immunodeficiency virus type 1 (HIV-1) envelope protein provides the primary contact between the virus and host, and is the main target of the adaptive humoral immune response. The length of gp120 variable loops and the number of N-linked glycosylation events are key determinants for virus infectivity and immune escape, while the V3 loop overall positive charge is known to affect co-receptor tropism. We selected two families in which both parents and two children had been infected with HIV-1 for nearly 10 years, but who demonstrated variable parameters of disease progression. We analysed the gp120 envelope sequence and compared individuals that progressed to those that did not in order to decipher evolutionary alterations that are associated with disease progression when individuals are infected with genetically related virus strains. The analysis of the V3-positive charge demonstrated an association between higher V3-positive charges with disease progression. The ratio between the amino acid length and the number of potential N-linked glycosylation sites was also shown to be associated with disease progression with the healthier family members having a lower ratio. In conclusion in individuals initially infected with genetically linked virus strains the V3-positive charges and N-linked glycosylation are associated with HIV-1 disease progression and follow varied evolutionary paths for individuals with varied disease progression.

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