Endocytic Host Cell Machinery Plays a Dominant Role in Intracellular Trafficking of Incoming Human Immunodeficiency Virus Type 1 in Human Placental Trophoblasts

ABSTRACT Vertical transmission of human immunodeficiency virus type 1 (HIV-1) is the primary cause of infection by this retrovirus in infants. In this study, we report for the first time that there is a correlation between endocytic uptake of HIV-1 and virus gene expression in polarized trophoblasts. To shed light on the relationship between endocytosis and the fate of HIV-1 in polarized trophoblasts, the step-by-step movements of HIV-1 within the endocytic compartments were tracked by confocal imaging. Incoming virions were initially located in early endosomes. As time progressed, virions accumulated in late endosomes. HIV-1 was also found in apical recycling endosomes and at the basolateral pole. Experiments performed with indicator cells revealed that HIV-1 is recycled and transcytosed. These data indicate that the intracellular trafficking of HIV-1 upon entry into polarized human trophoblasts is a complex process which requires the active participation of the endocytic host cell machinery.

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Impact of Natural Polymorphism within the gp41 Cytoplasmic Tail of Human Immunodeficiency Virus Type 1 on the Intracellular Distribution of Envelope Glycoproteins and Viral Assembly

Journal of Virology ◽

10.1128/jvi.01659-06 ◽

2006 ◽

Vol 81 (1) ◽

pp. 125-140 ◽

Cited By ~ 20

Author(s):

Marie Lambelé ◽

Béatrice Labrosse ◽

Emmanuelle Roch ◽

Alain Moreau ◽

Bernard Verrier ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Viral Replication ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Intracellular Trafficking ◽

Intracellular Distribution ◽

Immunodeficiency Virus ◽

Natural Polymorphism ◽

Hiv 1

ABSTRACT The motifs involved in the various functions of the human immunodeficiency virus type 1 (HIV-1) gp41 cytoplasmic tail (CT), particularly those related to the intracellular trafficking and assembly of envelope glycoproteins (Env) onto core particles, have generally been assessed with a restricted panel of T-cell laboratory-adapted virus strains. Here, we investigated gp41 CT sequences derived from individuals infected with HIV-1 viruses of various subtypes. We identified four patients harboring HIV variants with a natural polymorphism in the membrane-proximal tyrosine-based signal Y712SPL or the Y802W803 diaromatic motif, which are two major determinants of Env intracellular trafficking. Confocal microscopy showed that the intracellular distribution of Env with a mutation in the tyrosine or diaromatic motif differed from that of Env with no mutation in these motifs. Surprisingly, the gp41 CTs of the primary viruses also had differential effects on the intracellular distribution of Env, independently of mutations in the tyrosine or diaromatic motifs, suggesting the involvement of additional determinants. Furthermore, analyses of virus replication kinetics indicated that the effects of mutations in the tyrosine or diaromatic motifs on viral replication depended on the gp41 CT context. These effects were at least partly due to differences in the efficiency of Env incorporation into virions. Thus, polymorphisms in primary HIV-1 gp41 CTs at the quasispecies or subtype level can influence the intracellular distribution of Env, its incorporation into virions, and viral replication capacity.

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Post-translational intracellular trafficking determines the type of immune response elicited by DNA vaccines expressing Gag antigen of Human Immunodeficiency Virus Type 1 (HIV-1)

Human Vaccines & Immunotherapeutics ◽

10.4161/hv.26009 ◽

2013 ◽

Vol 9 (10) ◽

pp. 2095-2102 ◽

Cited By ~ 9

Author(s):

Aaron Wallace ◽

Kim West ◽

Alan Rothman ◽

Francis Ennis ◽

Shan Lu ◽

...

Keyword(s):

Immune Response ◽

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Intracellular Trafficking ◽

Dna Vaccines ◽

Immunodeficiency Virus ◽

Hiv 1

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Reciprocal Modulatory Interaction between Human Immunodeficiency Virus Type 1 Tat and Transcription Factor NFAT1

Molecular and Cellular Biology ◽

10.1128/mcb.19.5.3645 ◽

1999 ◽

Vol 19 (5) ◽

pp. 3645-3653 ◽

Cited By ~ 50

Author(s):

Fernando Macián ◽

Anjana Rao

Keyword(s):

Human Immunodeficiency Virus ◽

Transcription Factor ◽

Host Cell ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Cell Protein ◽

Amino Terminal ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) gene expression is regulated by interactions between both viral and host factors. These interactions are also responsible for changes in the expression of many host cell genes, including cytokines and other immune regulators, which may account for the state of immunological dysregulation that characterizes HIV-1 infection. We have investigated the role of a host cell protein, the transcription factor NFAT1, in HIV-1 pathogenesis. We show that NFAT1 interacts with Tat and that this interaction, which involves the major transactivation domain of NFAT1 and the amino-terminal region of Tat, results in a reciprocal modulatory interplay between the proteins: whereas Tat enhances NFAT1-driven transcription in Jurkat T cells, NFAT1 represses Tat-mediated transactivation of the HIV-1 long terminal repeat (LTR). Moreover, NFAT1 binds to the κB sites on the viral LTR and negatively regulates NF-κB-mediated activation of HIV-1 transcription, by competing with NF-κB1 for its binding sites on the HIV-1 LTR. Tat-mediated enhancement of NFAT1 transactivation may explain the upregulation of interleukin 2 and other cytokines that occurs during HIV-1 infection. We discuss the potentially opposing roles of NFAT1 and another family member, NFAT2, in regulating gene transcription of HIV-1 and endogenous cytokine genes.

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Glycosphingolipid Composition of Human Immunodeficiency Virus Type 1 (HIV-1) Particles Is a Crucial Determinant for Dendritic Cell-Mediated HIV-1 trans-Infection

Journal of Virology ◽

10.1128/jvi.02249-08 ◽

2009 ◽

Vol 83 (8) ◽

pp. 3496-3506 ◽

Cited By ~ 50

Author(s):

Steven C. Hatch ◽

Jacob Archer ◽

Suryaram Gummuluru

Keyword(s):

Human Immunodeficiency Virus ◽

Host Cell ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Fumonisin B1 ◽

Ceramide Synthase ◽

Immunodeficiency Virus ◽

Synthase Inhibitor ◽

Hiv 1

ABSTRACT Interactions of human immunodeficiency virus type 1 (HIV-1) with dendritic cells (DCs) are multifactorial and presumably require nonredundant interactions between the HIV-1 envelope glycoprotein gp120 and molecules expressed on the DC surface that define the cellular fate of the virus particle. Surprisingly, neutralization of HIV-1 gp120-dependent binding interactions with DCs was insufficient to prevent HIV-1 attachment. Besides gp120, HIV-1 particles also incorporate host cell-derived proteins and lipids in their particle membrane. In this study, we demonstrate a crucial role for host cell-derived glycosphingolipids (GSLs) for the initial interactions of HIV-1 particles with both immature and mature DCs. Production of HIV-1 particles from virus producer cells treated with ceramide synthase inhibitor fumonisin B1 or glucosylceramide synthase inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) resulted in the production of virus particles that, although capable of binding previously defined HIV-1 gp120-specific attachment factors CD4, DC-SIGN, and syndecans, were attenuated in their ability to be captured by both immature and mature DCs. Furthermore, GSL-deficient HIV-1 particles were inhibited in their ability to establish productive infections in DC-T-cell cocultures. These studies provide initial evidence for the role of HIV-1 particle membrane-associated GSLs in virus invasion of DCs and also provide additional novel cellular targets, GSL biosynthetic pathways and GSL-dependent HIV-1 interactions with DCs, for development of antiviral therapy.

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