HIV-1 gp120 N-linked glycosylation differs between plasma and leukocyte compartments

Ho, Yung Shwen; Abecasis, Ana; Theys, Kristof; Deforche, Koen; Dwyer, Dominic E.; Charleston, Michael A.; Vandamme, Anne‐Mieke; Saksena, Nitin K.

doi:10.1186/1743-422x-5-14

Cited by 15 publications

(16 citation statements)

References 27 publications

(43 reference statements)

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“…HIV-1, in particular, is reported to acquire distinct envelope glycosylation patterns of the producer cell (49), potently modulating the infectivity of progeny virions (50). Therefore, we evaluated whether the production of HIV-1 by different host cells affects the transcytosis efficiency of the virus through epithelial cells.…”

Section: Resultsmentioning

confidence: 99%

“…Cell-free HIV-1, along with cell-associated virus, is present in breast milk (9, 49) and semen (1, 24, 26) and thus available for transcytosis across recipient small intestinal and rectal columnar epithelium during vertical and homosexual transmission, respectively. Presumably, transcytosis through HT-29 model epithelium is initiated by viral envelope binding to the epithelial surface.…”

Section: Discussionmentioning

confidence: 99%

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GP41-Specific Antibody Blocks Cell-Free HIV Type 1 Transcytosis through Human Rectal Mucosa and Model Colonic Epithelium

Shen¹,

Drelichman

Bimczok³

et al. 2010

The Journal of Immunology

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Monostratified epithelial cells translocate HIV-1 from the apical to the basolateral surface via vesicular transcytosis. Since acutely transmitted HIV-1 is almost exclusively CCR5-tropic and human intestinal epithelial cells preferentially transcytose CCR5-tropic virus, we established epithelial monolayers using polarized HT-29 cells transduced to express CCR5, and an explant system using normal human rectal mucosa, to characterize biological parameters of epithelial cell transcytosis of HIV-1 and assess antiviral antibody blockade of transcytosis. The amount of cell-free HIV-1 transcytosed through the epithelial monolayer increased linearly in relation to the amount of virus applied to the apical surface, indicating transcytosis efficiency was constant (r2 = 0.9846, P<0.0001). The efficiency of HIV-1 transcytosis ranged between 0.05% and 1.21%, depending on the virus strain, producer cell type and gp120 V1-V3 loop signature. Inoculation of HIV-1 neutralizing antibodies to the immunodominant region (7B2) or the conserved membrane proximal external region (2F5) of gp41 or to cardiolipin (IS4) onto the apical surface of epithelial monolayers prior to inoculation of virus significantly reduced HIV-1 transcytosis. 2F5 was the most potent of these IgG1 mAbs. Dimeric IgA (dIgA) and monomeric IgA (mIgA), but not polymeric IgM, 2F5 antibodies also blocked HIV-1 transcytosis across the epithelium and, importantly, across explanted normal human rectal mucosa, with mIgA substantially more potent than dIgA in effecting transcytosis blockade. These findings underscore the potential role of transcytosis blockade in the prevention of HIV-1 transmission across columnar epithelium such as that of the rectum.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

GP41-Specific Antibody Blocks Cell-Free HIV Type 1 Transcytosis through Human Rectal Mucosa and Model Colonic Epithelium

Shen¹,

Drelichman

Bimczok³

et al. 2010

The Journal of Immunology

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“…29 In this study, Ho and co-workers analyzed a gp120 region spanning C2-V5 by aligning env protein sequences from 305 clones derived from plasma and other compartments in 15 individuals infected with HIV-1. 29 In the paper by Ho and collaborators there is no reference to the pattern of sequons in V4, supposedly due to the high degree of sequence variation and length polymorphism in this region. This may explain the apparent discordance in our data about compartmentalization.…”

Section: Discussionmentioning

confidence: 99%

The Polymorphic Nature of HIV Type 1envV4 Affects the Patterns of Potential N-Glycosylation Sites in Proviral DNA at the Intrahost Level

Bélair

Dovat

Foley

et al. 2009

AIDS Research and Human Retroviruses

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We have previously shown that env V4 from HIV-1 plasma RNA is highly heterogeneous within a single patient, due to indel-associated polymorphism. In this study, we have analyzed the variability of V4 in proviral DNA from unfractionated PBMC and sorted T and non-T cell populations within individual patients. Our data show that the degree of sequence variability and length polymorphism in V4 from HIV provirus is even higher than we previously reported in plasma. The data also show that the sequence of V4 depends largely on the experimental approach chosen. We could observe no clear trend for compartmentalization of V4 variants in specific cell types. Of interest is the fact that some variants that had been found to be predominant in plasma were not detected in any of the cell subsets analyzed. Consistently with our observations in plasma, V3 was found to be relatively conserved at both interpatient and intrapatient level. Our data show that V4 polymorphism involving insertions and deletions in addition to point mutations results in changes in the patterns of sequons in HIV-1 proviral DNA as well as in plasma RNA. These rearrangements may result in the coexistence, within the same individual, of a swarm of different V4 regions, each characterized by a different carbohydrate surface shield. Further studies are needed to investigate the mechanism responsible for the variability observed in V4 and its role in HIV pathogenesis.

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“…In a study by Ho et al on the frequency of N-linked glycosylation observed between 15 independent patients, the authors reported that the number of glycosylation sites was not consistent across the different compartments [10]. Plasma compartment viruses have a higher probability for glycosylation at the N-terminal of V4 and within C4 as compared with cellular compartment viruses (e.g., CD4 + T lymphocytes, CD8 + T lymphocytes, monocytes and PBMCs).…”

Section: Glycosylation Adaptation During Compartmentalizationmentioning

confidence: 96%

“…In addition, the specific presence of the glycosylation site in the C3 region can enhance virus fusogenicity and faster entry kinetics in CCR5 viruses [9]. Beyond the effect of glycosylation on receptor binding, glycans on gp120 can potentially influence the virus's ability to infect different cellular compartments during active infection [10], which assists the virus in evading the host immune system [11] and influences the efficiency of host-host transmission events [12]. In this review, we will mainly be focusing on the glycosylation of gp120 in order to determine its influence on HIV-1 compartmentalization, disease progression, viral evolution and gp120 structure modulation.…”

Section: Hiv-1 Envelope Glycoprotein and Its Glycosylationmentioning

confidence: 98%

Glycosylation in HIV-1 Envelope Glycoprotein and its Biological Implications

Saksena

2013

Future Virol.

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Glycosylation of HIV-1 envelope proteins (Env gp120/gp41) plays a vital role in viral evasion from the host immune response, which occurs through the masking of key neutralization epitopes and the presentation of the Env glycosylation as ‘self’ to the host immune system. Env glycosylation is generally conserved, yet its continual evolution plays an important role in modulating viral infectivity and Env immunogenicity. Thus, it is believed that Env glycosylation, which is a vital part of the HIV-1 architecture, also controls intra- and inter-clade genetic variations. Discerning intra- and inter-clade glycosylation variations could therefore yield important information for understanding the molecular and biological differences between HIV clades and may assist in effectively designing Env-based immunogens and in clearly understanding HIV vaccines. This review provides an in-depth perspective of various aspects of Env glycosylation in the context of HIV-1 pathogenesis.

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HIV-1 gp120 N-linked glycosylation differs between plasma and leukocyte compartments

Cited by 15 publications

References 27 publications

GP41-Specific Antibody Blocks Cell-Free HIV Type 1 Transcytosis through Human Rectal Mucosa and Model Colonic Epithelium

GP41-Specific Antibody Blocks Cell-Free HIV Type 1 Transcytosis through Human Rectal Mucosa and Model Colonic Epithelium

The Polymorphic Nature of HIV Type 1envV4 Affects the Patterns of Potential N-Glycosylation Sites in Proviral DNA at the Intrahost Level

Glycosylation in HIV-1 Envelope Glycoprotein and its Biological Implications

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