Hunting Down HIV-1 Gag Proteins at the Plasma Membrane of Human T Lymphocytes

2016 ◽  
Vol 32 (7) ◽  
pp. 658-659
Author(s):  
Charlotte Mariani-Floderer ◽  
Jean-Baptiste Sibarita ◽  
Cyril Favard ◽  
Delphine M. Muriaux
Keyword(s):  
Plasma Membrane ◽  
T Lymphocytes ◽  
Gag Proteins ◽  
Human T Lymphocytes ◽  
Hiv 1

scholarly journals HIV-1 requires Arf6-mediated membrane dynamics to efficiently enter and infect T lymphocytes

2011 ◽  
Vol 22 (8) ◽  
pp. 1148-1166 ◽  
Author(s):  
Laura García-Expósito ◽  
Jonathan Barroso-González ◽  
Isabel Puigdomènech ◽  
José-David Machado ◽  
Julià Blanco ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
T Lymphocytes ◽  
Viral Entry ◽  
Membrane Trafficking ◽  
Membrane Dynamics ◽  
Viral Fusion ◽  
Viral Attachment ◽  
Immunodeficiency Virus ◽  
Vesicular Stomatitis ◽  
Hiv 1

As the initial barrier to viral entry, the plasma membrane along with the membrane trafficking machinery and cytoskeleton are of fundamental importance in the viral cycle. However, little is known about the contribution of plasma membrane dynamics during early human immunodeficiency virus type 1 (HIV-1) infection. Considering that ADP ribosylation factor 6 (Arf6) regulates cellular invasion via several microorganisms by coordinating membrane trafficking, our aim was to study the function of Arf6-mediated membrane dynamics on HIV-1 entry and infection of T lymphocytes. We observed that an alteration of the Arf6–guanosine 5′-diphosphate/guanosine 5′-triphosphate (GTP/GDP) cycle, by GDP-bound or GTP-bound inactive mutants or by specific Arf6 silencing, inhibited HIV-1 envelope–induced membrane fusion, entry, and infection of T lymphocytes and permissive cells, regardless of viral tropism. Furthermore, cell-to-cell HIV-1 transmission of primary human CD4+T lymphocytes was inhibited by Arf6 knockdown. Total internal reflection fluorescence microscopy showed that Arf6 mutants provoked the accumulation of phosphatidylinositol-(4,5)-biphosphate–associated structures on the plasma membrane of permissive cells, without affecting CD4-viral attachment but impeding CD4-dependent HIV-1 entry. Arf6 silencing or its mutants did not affect fusion, entry, and infection of vesicular stomatitis virus G–pseudotyped viruses or ligand-induced CXCR4 or CCR5 endocytosis, both clathrin-dependent processes. Therefore we propose that efficient early HIV-1 infection of CD4+T lymphocytes requires Arf6-coordinated plasma membrane dynamics that promote viral fusion and entry.

Antiviral Effect of Ingenol and Gingerol During HIV-1 Replication in MT4 Human T Lymphocytes

2008 ◽  
Vol 78 (2) ◽  
pp. A44 ◽  
Author(s):  
Hak Sung Lee ◽  
Sung-Soon Kim ◽  
Gab Jung Kim ◽  
Joo-shil Lee ◽  
Eun-Jin Kim ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Antiviral Effect ◽  
Human T Lymphocytes ◽  
Hiv 1

scholarly journals Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly

2006 ◽  
Vol 103 (30) ◽  
pp. 11364-11369 ◽  
Author(s):  
J. S. Saad ◽  
J. Miller ◽  
J. Tai ◽  
A. Kim ◽  
R. H. Ghanam ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Virus Assembly ◽  
Structural Basis ◽  
Gag Proteins ◽  
Hiv 1

Inhibition of HIV-1 in human T-lymphocytes by retrovirally transduced anti-tat and rev hammerhead ribozymes

Gene ◽  
1994 ◽  
Vol 149 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Zhou Chen ◽  
Ingrid C. Bahner ◽  
Garry P. Larson ◽  
John A. Zaia ◽  
John J. Rossi ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Hammerhead Ribozymes ◽  
Human T Lymphocytes ◽  
Hiv 1

scholarly journals Live-Cell Coimaging of the Genomic RNAs and Gag Proteins of Two Lentiviruses

2010 ◽  
Vol 84 (13) ◽  
pp. 6352-6366 ◽  
Author(s):  
Iris Kemler ◽  
Anne Meehan ◽  
Eric M. Poeschla
Keyword(s):  
Plasma Membrane ◽  
Nuclear Envelope ◽  
Spatial Dynamics ◽  
Live Cells ◽  
Genomic Rna ◽  
Genomic Rnas ◽  
Gag Proteins ◽  
Immunodeficiency Virus ◽  
Genome Association ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) Gag and genomic RNA determinants required for encapsidation are well established, but where and when encapsidation occurs in the cell is unknown. We constructed MS2 phage coat protein labeling systems to track spatial dynamics of primate and nonprimate lentiviral genomic RNAs (HIV-1 and feline immunodeficiency virus [FIV]) vis-à-vis their Gag proteins in live cells. Genomic RNAs of both lentiviral genera were observed to traffic into the cytoplasm, and this was Rev dependent. In transit, FIV Gag and genomic RNA accumulated independently of each other at the nuclear envelope, and focal colocalizations of genomic RNA with an intact packaging signal (ψ) and Gag were observed to extend outward from the cytoplasmic face. In contrast, although HIV-1 genomic RNA was detected at the nuclear envelope, HIV-1 Gag was not. For both lentiviruses, genomic RNAs were seen at the plasma membrane if and only if Gag was present and ψ was intact. In addition, HIV-1 and FIV genomes accumulated with Gag in late endosomal foci, again, only ψ dependently. Thus, lentiviral genomic RNAs require specific Gag binding to accumulate at the plasma membrane, packaged genomes cointernalize with Gag into the endosomal pathway, and plasma membrane RNA incorporation by Gag does not trigger committed lentiviral particle egress from the cell. Based on the FIV results, we hypothesize that the Gag-genome association may initiate at the nuclear envelope.

scholarly journals HIV-1 Nef and Vpu Interfere with L-Selectin (CD62L) Cell Surface Expression To Inhibit Adhesion and Signaling in Infected CD4+T Lymphocytes

2015 ◽  
Vol 89 (10) ◽  
pp. 5687-5700 ◽  
Author(s):  
Lia Vassena ◽  
Erica Giuliani ◽  
Herwig Koppensteiner ◽  
Sebastian Bolduan ◽  
Michael Schindler ◽  
...  
Keyword(s):  
T Cells ◽  
Plasma Membrane ◽  
T Lymphocytes ◽  
Cell Surface ◽  
Immune Responses ◽  
Lymph Nodes ◽  
Viral Proteins ◽  
Peripheral Lymph ◽  
Leukocyte Homing ◽  
Hiv 1

ABSTRACTLeukocyte recirculation between blood and lymphoid tissues is required for the generation and maintenance of immune responses against pathogens and is crucially controlled by the L-selectin (CD62L) leukocyte homing receptor. CD62L has adhesion and signaling functions and initiates the capture and rolling on the vascular endothelium of cells entering peripheral lymph nodes. This study reveals that CD62L is strongly downregulated on primary CD4+T lymphocytes upon infection with human immunodeficiency virus type 1 (HIV-1). Reduced cell surface CD62L expression was attributable to the Nef and Vpu viral proteins and not due to increased shedding via matrix metalloproteases. Both Nef and Vpu associated with and sequestered CD62L in perinuclear compartments, thereby impeding CD62L transport to the plasma membrane. In addition, Nef decreased total CD62L protein levels. Importantly, infection with wild-type, but not Nef- and Vpu-deficient, HIV-1 inhibited the capacity of primary CD4+T lymphocytes to adhere to immobilized fibronectin in response to CD62L ligation. Moreover, HIV-1 infection impaired the signaling pathways and costimulatory signals triggered in primary CD4+T cells by CD62L ligation. We propose that HIV-1 dysregulates CD62L expression to interfere with the trafficking and activation of infected T cells. Altogether, this novel HIV-1 function could contribute to virus dissemination and evasion of host immune responses.IMPORTANCEL-selectin (CD62L) is an adhesion molecule that mediates the first steps of leukocyte homing to peripheral lymph nodes, thus crucially controlling the initiation and maintenance of immune responses to pathogens. Here, we report that CD62L is downmodulated on the surfaces of HIV-1-infected T cells through the activities of two viral proteins, Nef and Vpu, that prevent newly synthesized CD62L molecules from reaching the plasma membrane. We provide evidence that CD62L downregulation on HIV-1-infected primary T cells results in impaired adhesion and signaling functions upon CD62L triggering. Removal of cell surface CD62L may predictably keep HIV-1-infected cells away from lymph nodes, the privileged sites of both viral replication and immune response activation, with important consequences, such as systemic viral spread and evasion of host immune surveillance. Altogether, we propose that Nef- and Vpu-mediated subversion of CD62L function could represent a novel determinant of HIV-1 pathogenesis.

scholarly journals Cell-Type-Dependent Targeting of Human Immunodeficiency Virus Type 1 Assembly to the Plasma Membrane and the Multivesicular Body

2004 ◽  
Vol 78 (3) ◽  
pp. 1552-1563 ◽  
Author(s):  
Akira Ono ◽  
Eric O. Freed
Keyword(s):  
Human Immunodeficiency Virus ◽  
Plasma Membrane ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Multivesicular Body ◽  
Cell Type ◽  
Gag Proteins ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) assembly-and-release pathway begins with the targeting of the Gag precursor to the site of virus assembly. The molecular mechanism by which Gag is targeted to the appropriate subcellular location remains poorly understood. Based on the analysis of mutant Gag proteins, we and others have previously demonstrated that a highly basic patch in the matrix (MA) domain of Gag is a major determinant of Gag transport to the plasma membrane. In this study, we determined that in HeLa and T cells, the MA mutant Gag proteins that are defective in plasma membrane targeting form virus particles in a CD63-positive compartment, defined as the late endosome or multivesicular body (MVB). Interestingly, we find that in primary human macrophages, both wild-type (WT) and MA mutant Gag proteins are targeted specifically to the MVB. Despite the fact that particle assembly in macrophages occurs at an intracellular site rather than at the plasma membrane, we observe that WT Gag expressed in this cell type is released as extracellular virions with high efficiency. These results demonstrate that Gag targeting to and assembly in the MVB are physiologically important steps in HIV-1 virus particle production in macrophages and that particle release in this cell type may follow an exosomal pathway. To determine whether Gag targeting to the MVB is the result of an interaction between the late domain in p6Gag and the MVB sorting machinery (e.g., TSG101), we examined the targeting and assembly of Gag mutants lacking p6. Significantly, the MVB localization of Gag was still observed in the absence of p6, suggesting that an interaction between Gag and TSG101 is not required for Gag targeting to the MVB. These data are consistent with a model for Gag targeting that postulates two different cellular binding partners for Gag, one on the plasma membrane and the other in the MVB.

scholarly journals Human Immunodeficiency Virus Type 1 Gag Contains a Dileucine-Like Motif That Regulates Association with Multivesicular Bodies

2004 ◽  
Vol 78 (11) ◽  
pp. 6013-6023 ◽  
Author(s):  
O. Wolf Lindwasser ◽  
Marilyn D. Resh
Keyword(s):  
Human Immunodeficiency Virus ◽  
Plasma Membrane ◽  
Human Immunodeficiency Virus Type ◽  
Particle Production ◽  
Endocytic Pathway ◽  
Multivesicular Bodies ◽  
Gag Proteins ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Multivesicular bodies (MVBs) are cholesterol-enriched organelles formed by the endocytic pathway. The topology of vesicle formation in MVBs is identical to that of retroviral budding from the plasma membrane, and budding of human immunodeficiency virus type 1 (HIV-1) into MVBs in macrophages has recently been visualized. The Gag proteins from HIV-1, as well as many other retroviruses, contain short motifs that mediate interactions with MVBs and other endocytic components, suggesting that Gag proteins directly interface with the endocytic pathway. Here, we show that HIV-1 Gag contains an internalization signal that promotes endocytosis of a chimeric transmembrane fusion protein. Mutation of this motif within Gag strongly inhibits virus-like particle production. Moreover, wild-type Gag, but not the internalization-defective mutation, can be induced to accumulate within CD63-positive MVBs by treatment of cells with U18666A, a drug that redistributes cholesterol from the plasma membrane to MVBs. We propose that HIV-1 Gag contains a signal that promotes interaction with the cellular endocytic machinery and that the site of particle production is regulated by the subcellular distribution of cholesterol.

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