M184V is a primary mutation that causes resistance to the Drug 3TC, which is a c
ID: 86928 • Letter: M
Question
M184V is a primary mutation that causes resistance to the Drug 3TC, which is a chain terminator directed toward HIV-1 RT. However, to get to M184V, the enzyme must go through M184I variant. Yet, M184I is never seen in patients. Explain what must happen in the RT to get to M184V from M184 and why do you think M184I is never seen in patients, though it had to have been around for at least a short period of time. This question is more of a conceptual question based on everything we have covered so far in class and in activity. So, really think about this one.Explanation / Answer
Although considerable progress has been made in the treatment of human immunodeficiency virus type 1 (HIV-1)-associated disease, the emergence of mutated variants of HIV-1 that are resistant to antiviral drugs represents a major problem.
The prolonged use of drugs that are nucleoside analog chain terminators such as 2,3-dideoxy-3-thiacytidine (3TC) results in providing the resistant to the viruses that contain mutations in the RT enzyme.
M184I variant is disappeared from the population of the virus because of the outgrowth of M184V variant. It has been discovered that M184V(GTG) originates from wild-type Met (ATG) and not from the M184I variant (ATA).
When the sequence at the M184 is mutagenized to get M184V, it results in viral attenuation or nonviability. This also diminished the function of RT enzyme. The substitution in M184V causes changes in the geometry of the YMDD (Tyrosine-methionine-aspartate-aspartate) motif which is conserved in all retroviruses.
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