Effects Of Hiv-1 Pathogenesis

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In the absence of a cure for HIV Type 1 (HIV-1) pathogenesis, highly active antiretroviral therapy (HAART) are designed to suppress viral replication and maintain it at low to undetectable levels (Prabu-Jeyabalan et al, 2002). Due to their high intrinsic antiviral activity, the introduction of HIV-1 protease inhibitors (PIs) have led to a dramatic reduction in morbidity and mortality rates of HIV-1 infected patients (Codoner et al, 2017). HIV-1 protease inhibitors are peptidomimetics, or substrate or transition state analogs that mimic natural peptides or proteins and retain the ability to interact with the original protein’s biological target, that competitively targets the hydrophobic P2-P2’ domain in the active site (Prabu-Jeyabalan et…show more content…
Proteolytic processing of the Gag polyprotein results mature HIV-1 structural proteins: p17 matrix (MA), p24 capsid (CA), p7 nucleocapsid (NC), p6 domains, and two spacer peptides, SP1 and SP2. Each of these HIV-1 structural proteins play a crucial role in the HIV-1 retroviral replication cycle. MA is responsible for targeting Gag to the plasma membrane and promoting the incorporation of viral envelop glycoproteins into the forming virions; CA drives Gag multimerization during assembly to form the Gag lattice that encapsidates the viral RNA genome; NC recruits the viral RNA genome into the virions; and the p6 domain recruits the endosomal sorting complex required for transport (ESCRT) apparatus that catalyzes the membrane fission step responsible for the budding off of new virions from the infected cell (Freed, 2015).
Due to the infidelity of HIV-1 reverse transcriptase, HIV-1 protease, as with all other HIV proteins, undergoes frequent mutation (Prabu-Jeyabalan et al, 2002). Despite the high genetic barrier, or sufficient number of critical drug-resistance mutations to overcome the anti-HIV activity of a drug regimen, of PI, selective pressure induced by PIs have been seen to be associated with drug resistance mutations at both the active site of HIV-1 protease and Gag polyprotein (Codoner et al,
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