(Chapter 11) Virus-modified exosomes have been proposed for targeted nucleotide
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Question
(Chapter 11) Virus-modified exosomes have been proposed for targeted nucleotide delivery to cells as shown below:
A) Describe the molecular composition of virus-modified exosomes
B) Compare the composition to a typical eukaryotic cell membrane & describe the function of different molecules
C) Describe what you deliver with this molecule and how it would function
Viral and cellul components elective Virus-modified exosomes "stuffed" with selected viral and/or cellular components MVB Virus-modified eo a exOSO mes Cytoplasm EBVExplanation / Answer
Ans1:
Exosomes are small vesicles secreted from cells that participate in intercellular communication events. Accumulating evidence demonstrates that host exosome pathways are hijacked by viruses and that virally modified exosomes contribute to virus spread and immune evasion. Latent membrane protein 1 (LMP1) is the major viral oncogene expressed in most EBV-associated cancers and is essential for the proliferation program and B cell immortalization.
Molecular composition of virus-modified exosomes
LMP (Latent membrane protein 1) is a viral protein that has emerged as a key mediator of the components of exosomes and their functions in intracellular communications.
FGF-2, a potent angiogenic factor, was the first protein whose exosomal secretion was demonstrated to be influenced by LMP1 expression.
EGFR: (Epidermal growth factor receptor) and phosphoinositol 3-kinase (PI3K), two proteins frequently activated in cancers and important for LMP1-mediated transformation, were later observed in nasopharyngeal carcinoma cells latently infected with EBV (Epstin Brar Visruse).
Other molecules enriched in LMP1-positive exosomes included major histocompatibility complex (MHC) class I and II molecules, tumor necrosis factor (TNF) receptor-associated factor 2 and NF-B-induced kinase (TNIK), the Fgr kinase, the p85 regulator unit of PI3K, intercellular adhesion molecule 1 (ICAM1), ezrin, annexins, Rab GTPases, ARF6, integrins, flotillin 1 and 2, growth factor receptor-bound protein 2 (GRB2), neuroblastoma RAS viral oncogene homolog (NRAS), Lyn, mitogen-activated protein kinase 1 (MAPK1), RAC2, and PIP4K2A .
Ans: Typical eukaryotic cell membrane & the function of different molecules
· The cell membrane (also known as the plasma membrane or cytoplasmic membrane) is a biological membrane that separates the interior of all cells from the outside environment.
· The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. The basic function of the cell membrane is to protect the cell from its surroundings.
· It consists of the phospholipid bilayer with embedded proteins. Cell membranes are involved in a variety of cellular processes such as cell adhesion, ion conductivity and cell signalling and serve as the attachment surface for several extracellular structures, including the cell wall, glycocalyx, and intracellular cytoskeleton. Cell membranes can beartificially reassembled.
· Exocytosis is the process by which a cell moves the contents of secretory vesicles out of the cell via the cell membrane.
· Endocytosis is the opposite process by which the contents of secretory vesicles are moved into the cell via the cell membrane.
· Proteins called surface protein markers embedded in the cell membrane identify the cell, enabling nearby cells to communicate with each other.
· Cell membranes often include receptor sites for interaction with specific biochemicals such as certain hormones, neurotransmitters and immune proteins. In this way the cell can recognize and process some signals received from the extracellular environment.
Ans 3: Functions of Virus-modified exosomes
LMP1: was discovered to be secreted from EBV-infected cancer cells in exosomes, resulted in altering the immune response. Specifically, a conserved region within the first transmembrane domain of LMP1 was found to exhibit immunosuppressive effects by inducing T cell energy.
FGF-2: a potent angiogenic factor which induces the expression of LMP1.
EGFR, and PI3K are efficiently taken up by uninflected cells through paracrine mechanisms, leading to the activation of AKT and extracellular signal-regulated kinase (ERK) signaling pathways in the recipient cells
Molecules enriched in LMP1-positive exosomes included major histocompatibility complex (MHC) class I and II molecules, tumor necrosis factor (TNF) receptor-associated factor 2 and NF-B-induced kinase (TNIK), the Fgr kinase, the p85 regulator unit of PI3K, intercellular adhesion molecule 1 (ICAM1), ezrin, annexins, Rab GTPases, ARF6, integrins, flotillin 1 and 2, growth factor receptor-bound protein 2 (GRB2), neuroblastoma RAS viral oncogene homolog (NRAS), Lyn, mitogen-activated protein kinase 1 (MAPK1), RAC2, and PIP4K2A. LMP1-modified exosomes would affect molecular and cellular functions of cell growth and proliferation, cellular movement, cell death and survival, development, and cell-to-cell signaling. LMP1-modified exosomes do indeed enhance proliferation, migration, invasion, and B cell differentiation toward a plasmablast-like phenotype when incubated with noninfected cells. The significance of exosomes in oncogenicity was recently demonstrated in breast cancer, where nontransformed cells were found to form tumors in mice when incubated with exosomes from malignant cells or the blood of patients alone.
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