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.
-As it matures, the endosomal lumen becomes acidified relative to the cytosol. Protons from the cytosol most likely enter the endosomal lumen by which of the following processes?

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.
-As it matures, the endosomal lumen becomes acidified relative to the cytosol. Protons from the cytosol most likely enter the endosomal lumen by which of the following processes?

Quizplus · Accepted Answer

11ecba2d_0ff0_3e47_a3bf_ab286dcb6db7_MD0008_00 In the absence of external energy input, molecules in solution diffuse from areas of high concentration to low concentration. Such flow down a concentration gradient is thermodynamically favorable. Molecules that are separated from an area of low concentration by a membrane will still flow across the membrane down their concentration gradient as long as the membrane is permeable to those molecules. For molecules to move against their concentration gradient, energy must be put into the system because the process is thermodynamically unfavorable. Transport systems that require energy input and move substances against their concentration gradient are active transport systems. Acidification of the endosomal lumen as it matures from an early endosome to a late endosome involves the transport of protons against their concentration gradient from an area of relatively low concentration (cytosol; pH ≈ 7.4) to one of relatively high concentration (endosomal lumen; pH ≈ 5.5). Therefore, protons from the cytosol can only enter the endosomal lumen if energy is added to the system. (Choices A, B, and C) Facilitated diffusion and simple diffusion are both forms of passive transport, in which no energy input is required and molecules diffuse down their concentration gradient. In simple diffusion, molecules that are small or lipid-soluble travel across the cell membrane directly, without help from protein channels. In facilitated diffusion, molecules that cannot normally cross the membrane on their own due to charge or size are allowed to pass through protein channels or gates that do not require energy input to operate. Educational objective: Molecules can cross biological membranes by active or passive transport. Active transport involves a molecule moving against its concentration gradient and requires energy input (eg, ATP). In contrast, passive transport involves molecules diffusing down their concentration gradient and requires no external energy. Passive transport can be divided into simple diffusion, in which molecules cross membranes directly, and facilitated diffusion, in which molecules must go through protein channels.

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