Passage
Adeno-associated virus 2 (AAV2) is a nonpathogenic, nonenveloped DNA virus that requires helper viruses such as adenovirus (AV) or herpes simplex virus (HSV) to replicate efficiently. Because it can transduce human cells, including quiescent (nondividing) cells, without causing disease, AAV2 is attractive as a gene therapy vector. In clinical trials, a modified AAV2 virus has successfully treated the retinal disease Leber's congenital amaurosis as well as the blood clotting disorder hemophilia B. AAV2 transduces cells via a multistep process, shown in Figure 1.
Figure 1 Schematic showing the mechanism of transduction by AAV2Studies indicate that unlike AV and HSV, AAV2 inhibits pathways other than the endosomal pathway, such as trafficking to the Golgi, increasing the percentage of invading virus particles that arrive at the nucleus.
Adapted from Xiao PJ, Samulski RJ. Cytoplasmic trafficking, endosomal escape, and perinuclear accumulation of adeno-associated virus type 2 particles are facilitated by microtubule network. J Virol. 2012;86(19) :10462-73.
-Which of the following is true concerning the proteins to which AAV2 binds in Figure 1, Step 1?

Question

Passage
Adeno-associated virus 2 (AAV2) is a nonpathogenic, nonenveloped DNA virus that requires helper viruses such as adenovirus (AV) or herpes simplex virus (HSV) to replicate efficiently. Because it can transduce human cells, including quiescent (nondividing) cells, without causing disease, AAV2 is attractive as a gene therapy vector. In clinical trials, a modified AAV2 virus has successfully treated the retinal disease Leber's congenital amaurosis as well as the blood clotting disorder hemophilia B. AAV2 transduces cells via a multistep process, shown in Figure 1.

Figure 1 Schematic showing the mechanism of transduction by AAV2Studies indicate that unlike AV and HSV, AAV2 inhibits pathways other than the endosomal pathway, such as trafficking to the Golgi, increasing the percentage of invading virus particles that arrive at the nucleus.
Adapted from Xiao PJ, Samulski RJ. Cytoplasmic trafficking, endosomal escape, and perinuclear accumulation of adeno-associated virus type 2 particles are facilitated by microtubule network. J Virol. 2012;86(19) :10462-73.
-Which of the following is true concerning the proteins to which AAV2 binds in Figure 1, Step 1?

Quizplus · Accepted Answer

11ecba2d_0fef_2cd5_a3bf_cbf896e091f8_MD0008_00 The membrane of an animal cell is described by the fluid mosaic model, in which transmembrane proteins and other components reside in a fluid bilayer composed largely of phospholipids. The cell membrane is said to be fluid as its various nonphospholipid components are able to migrate laterally through the entire phospholipid-rich surface of the cell in any direction. These other important components include cholesterol, glycoproteins, and glycolipids (proteins and lipids that have been modified with carbohydrates). Many membrane proteins, called transmembrane proteins, span the width of the membrane. Figure 1 shows that AAV2 binds to transmembrane proteins, which must be able to migrate laterally through the phospholipid environment of the cell membrane. (Choice A) Although it is believed that transmembrane proteins often localize to relatively ordered portions of the membrane called lipid rafts, these rafts are high in cholesterol content. In addition, the passage gives no information about the structure of the AAV2 transmembrane receptor, so specifics of its location within the cell membrane cannot be determined. (Choice B) Cytoskeletal components such as actin filaments interact with some transmembrane proteins, but they do not hold these proteins statically in place. Therefore, these transmembrane proteins can move dynamically within the cell membrane. (Choice C) The phospholipid bilayer of the cell membrane has an outer leaflet that interacts with the extracellular environment and an inner leaflet that interacts with the cytoplasm of the cell. Transmembrane proteins cross the entire phospholipid bilayer and therefore interact with both the outer and inner leaflets. Proteins that interact with only one leaflet are not transmembrane proteins. Educational objective: Cell membranes are composed largely of phospholipids, which act as a fluid that allows other membrane components such as transmembrane proteins, glycoproteins, cholesterol, and glycolipids to migrate through this environment laterally. Accordingly, the structure of the animal cell membrane is known as the fluid mosaic model.

Passage Adeno-Associated Virus 2 (AAV2) Is a Nonpathogenic, Nonenveloped DNA Virus