HIV-1 polymerase polyprotein (Pol) (Pol)

The HIV-1 polymerase polyprotein, encoded by the pol gene, is a multifunctional precursor essential for the replication and maturation of the Human Immunodeficiency Virus type 1 [1]. It is expressed as a Gag-Pol fusion protein through a ribosomal frameshift and is subsequently processed by the viral protease into three distinct enzymes: protease (PR), reverse transcriptase (RT), and integrase (IN) [2]. Reverse transcriptase converts the viral RNA genome into double-stranded DNA, while integrase facilitates the insertion of this DNA into the host cell's genome [3]. The protease is responsible for cleaving the Gag and Gag-Pol polyproteins into functional structural and enzymatic proteins, a step vital for the production of infectious virions [4]. Due to its indispensable role in the viral life cycle, the Pol polyprotein and its derived enzymes are the primary targets of modern antiretroviral therapy (ART) [3]. Drugs such as reverse transcriptase inhibitors, integrase strand transfer inhibitors, and protease inhibitors are used in combination to suppress viral replication and prevent the progression to AIDS [5]. Resistance to these drugs often arises through specific mutations within the pol gene, necessitating continuous monitoring and the development of next-generation inhibitors [1].

Other names

HIV-1 pol gene productGag-Pol polyproteinPolymerase polyproteinReverse transcriptase-protease-integrase polyprotein

Inhibition of reverse transcription (via chain termination or allosteric inhibition), inhibition of viral DNA integration into the host genome, and inhibition of proteolytic cleavage of viral polyproteins.