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Extracell Vesicles Circ Nucleic Acids 2020;1:20-56 I http://dx.doi.org/10.20517/evcna.2020.10 Page 33
3 Basic Research Laboratory National Cancer Institute, Frederick, MD, USA.
4 Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
Abstracts: Despite the emergence of combinational antiretroviral therapy (cART), 50% of all HIV-1
infected patients demonstrate some degree of HIV-1 associated neurocognitive disorder ranging from
asymptomatic neurocognitive impairment to mild neurocognitive disorder to severe HIV-associated
dementia. Although cART is highly effective in suppressing viremia, the lack of an FDA approved viral
transcription inhibitor allows for persistent non-processive transcription which results in the production
[1,2]
of short non-coding RNAs (TAR and TAR-gag) . Our lab and others have previously shown that these
RNAs are released from the cell in extracellular vesicles (EVs), specifically exosomes, and can induce
[3,4]
production of proinflammatory cytokines in recipient myeloid cells ; a factor that may contribute to
the neuroinflammation observed in HIV-1 infected individuals with HIV associated neurocognitive
disorder (HAND). Here, we have screened a panel of small molecules that have been previously found to
noncanonically bind HIV-1 Trans Activation Response (TAR) element, a 5’ RNA element that is required
[5]
for activated viral transcription . We have identified 5 candidates that effectively inhibit viral transcription
in myeloid and T-cells without toxicity. The mechanism of inhibition may be directly linked to Tat-activated
transcription and epigenetics modification. These data also suggest a direct link and communication
between Nuclear Transcription and EV cargo biogenesis. Collectively, our results suggest that the use
of small RNA-binding molecules to inhibit viral transcription could potentially be used to complement
existing cART drugs to address the current therapeutic gap in current regimens.

REFERENCES
1. Barclay RA, Schwab A, DeMarino C, et al. Exosomes from uninfected cells activate transcription of latent HIV-1. J Biol Chem
2017;292:14764.
2. Akpamagbo YA, DeMarino C, Pleet ML, et al. HIV-1 transcription inhibitors increase the synthesis of viral non-coding RNA that
contribute to latency. Curr Pharm Des 2017;23:4133-44.
3. Sampey GC, Saifuddin M, Schwab A, et al. Exosomes from HIV-1-infected cells stimulate production of pro-inflammatory cytokines
through trans-activating response (TAR) RNA. J Biol Chem 2016;291:1251-66.
4. DeMarino C, Pleet ML, Cowen M, et al. Publisher correction: antiretroviral drugs alter the content of extracellular vesicles from HIV-1-
infected cells. Sci Rep 2018;8:14303.
5. Abulwerdi FA, Shortridge MD, Sztuba-Solinska J, et al. Development of small molecules with a noncanonical binding mode to HIV-1
trans activation response (TAR) RNA. J Med Chem 2016;59:11148-60.

17. Extracellular vesicles and microRNAs in maternal milk are important for growth and gut
health during weaning in murine pups

Authors: Janos Zempleni. Mahrou Sadri, Fang Zhou
E-mail: jzempleni2@unl.edu
Affiliations: Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE,
USA.
Abstracts:
Background: Human milk contains approximately 2.2×10(exp)11 exosome-size EVs per mL, which
harbor more than 200 microRNAs. Mammals absorb EVs and microRNAs from milk, and microRNAs
regulate approximately 60% of human genes. Studies in transgenic mice suggest that EVs in maternal milk
accumulate primarily in the liver, brain and gastrointestinal (GI) mucosa in neonate pups.
Objective: Assess whether maternal EVs and microRNAs promote postnatal growth and GI health in
neonate mice.
Methods: WT pups were fostered to homozygous Tsg101 KO dams (impaired exosome biogenesis),
heterozygous Dicer KO dams (loss of microRNA biogenesis) or WT dams (control) from synchronized