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. 2018 Jun;163(6):1683-1689.
doi: 10.1007/s00705-018-3737-6. Epub 2018 Feb 10.

Tetraspanin blockage reduces exosome-mediated HIV-1 entry

Brian Sims  1   2 , Anitra L Farrow  3 , Sparkle D Williams  1 , Anju Bansal  3 , Alexandre Krendelchtchikov  1   3 , Qiana L Matthews  4   5
Affiliations

Tetraspanin blockage reduces exosome-mediated HIV-1 entry

Brian Sims et al. Arch Virol. 2018 Jun.

Abstract

HIV-1 is one of the most studied retroviruses. The role of exosomes in HIV-1 entry and pathogenesis are beginning to be appreciated. Exosomes can incorporate host proteins that are also contained in viruses (e.g., tetraspanins).

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Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the Institutional Review Board for the Protection of Human Subjects in Research at the University of Alabama at Birmingham (UAB) in accordance with approved guidelines and protocol. Breast milk was collected from samples prior to being discarded at the UAB Regional Newborn Intensive Care Unit with expedited IRB approval. Blood donors provided written informed consent prior to donation.

Conflict interest

The authors have no conflicts of interest to disclose.

Availability of data and material

Please contact author for data requests.

Figures

Fig. 1
Fig. 1
Western blot and nanoparticle tracking analysis (NTA) validation of exosomal samples. Western blots of plasma exosomes, breast milk exosomes, and 293 exosomes. 60 μg/lane, were probed with (A) anti-CD81 or anti-clathrin (B). Arrows indicate proteins of interest. NTA-generated size and concentration plots for (C) human plasma and (D) human breast milk-derived exosomes. The different colors lines represent different pools of exosomes
Fig. 2
Fig. 2
Exosomes significantly enhance HIV-1 entry into a human T cell line. A3R5.7 cells were seeded at a density of 1x105 cells/well with the addition of 5 µg/ml diethylaminoethyl-dextran [9, 24]. Virus was used at a multiplicity of infection (MOI) of 0.002. Virus entry into A3R5.7 cells was evaluated in the presence or absence of (A) plasma-derived exosomes (0.05 μg) (B) breast milk-derived exosomes (0.035 μg) or (C) 293-derived exosomes (0.1 μg). Viral entry was also evaluated in the presence of exosomes and anti-CD81 antibody (0.2 µg/well). All incubations were processed for one hour. Viral gene expression in all control and treatment groups was assessed by Renilla luciferase activity at 72 h post-infection. This time point was selected because we previously observed that it allows for optimal expression in a variety of cell types, including those in the present experiments. All conditions are identical through the following experiments unless otherwise noted
Fig. 3
Fig. 3
Exosomes significantly enhance HIV-1 entry into a human macrophage cell line. THP2574 cells (1x104 cells/well) were classically differentiated into macrophages with 1 ng/ml phorbol 12-myristate 13-acetate) for 96 h. Virus was used in THP2574 cells at an MOI of 0.18. Virus entry into THP2574 cells was evaluated in the presence or absence of (A) plasma-derived exosomes, (plasma exo) (B) breast milk-derived exosomes, (BM exo) or (C) 293-derived exosomes (293 exo). Viral entry was also evaluated in the presence of exosomes and anti-CD81 antibody
Fig. 4
Fig. 4
Breast milk-derived exosomes significantly enhance HIV-1 entry into human immune cell lines. Virus entry into (A) A3R5.7 cells or (B) THP2574 cells was evaluated in the presence or absence of breast milk-derived exosomes (BM exo). Viral entry was also evaluated in the presence of exosomes and anti-CD9 antibody
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References

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