what kind of drug could you design to stop HIV budding and thus spread of the vi
ID: 1837410 • Letter: W
Question
what kind of drug could you design to stop HIV budding and thus spread of the virus in the body?
The human immunodeficiency virus (HIV) is an enveloped retrovirus that buds from the plasma membrane of infected cells in a process driven by viral Gag protein, the major structural component of completed virus particles Gag protein binds to the plasma membrane of an infected cell and 4000 Gag molecules polymerize into a spherical shell, producing a structure that looks like a vesicle bud protruding outward from the plasma membrane Mutational studies with HIV have revealed that the N-terminal segment of Gag protein is required for association with the plasma membrane, whereas the C-terminal segment is required for pinching off of complete HIV particles For instance, if the portion of the viral genome encoding the C-terminus of Gag is removed, HIV buds will form in infected cells, but pinching off does not occur, and thus no free virus particles are released. The first indication that HIV budding employs the same molecular machinery as vesicle budding into endosomes came from the observation that Tsg101 an ESCRT protein, binds to the C-terminus of Gag protein. Subsequent findings have clearly established the mechanistic parallels between the two processes. For example, Gag is ubiquitinated as part of the process of virus budding, and in cells with mutations in Tsg101 or Vps4, HIV virus buds accumulate but cannot pinch off from the membrane (Figure 14-34) Moreover, when a segment from the cellular Hrs protein is added to a truncated Gag protein by construction of the appropriate hybrid gene, proper budding and release of virus particles is restored. Taken together, these results indicate that Gag protein mimics the function of Hrs, redirecting ESCRT proteins to the plasma membrane, where they can function in the budding of virus particlesExplanation / Answer
The prime feature of the drug has to be:
(i) stop the spread of the virus in human body.
In the given article the important steps of HIV's life cycle has been described. At each step,
it is theretically possible to design a drug that will stop the virus. Eg:
(a) a drug to prevent the entry of HIV into the human cell.
(b) a drug to destry the N terminus of the gag protein so that HIV cannot
attack the plasma membrane of the infected cell and polymerize.
or (c) a drug that will destroy the Gag protein complete.
However, it appears that a more practical way to designing a drug to prevent HIV can be
achieved by considering the following fact that in cells with mutations Tsg 101 or Vps4, the HIv accumulates but cannot pinch off. But addition of cellular Hrs protein can restore the process.
Hence , a drug that can
(i) invoke the desired Tsg101 or Vps4 mutation will be able to prevent HIV spreading & further budding
(ii) along with prevents the addition of HRS protein to then truncated Gag protein,
needs to be designed to sto the HIV budding and thus the spread of vitus.
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