HIV integrase strand transfer inhibitors (INSTIs) like raltegravir and dolutegravir block a specific step in the HIV replication cycle. The HIV integrase enzyme catalyses which two sequential reactions?

• A 3'-processing (endonucleolytic removal of two nucleotides from each 3' end of viral DNA) and strand transfer (insertion of processed viral DNA ends into host chromosome) ✓
• B Reverse transcription of genomic RNA to double-stranded DNA and nuclear import of the pre-integration complex
• C Cleavage of the Gag-Pol polyprotein precursor and dimerization of mature viral particles
• D Template switching between two RNA strands to generate recombinant proviral DNA

Explanation

HIV integrase catalyses two sequential reactions: (1) 3'-processing — in the cytoplasm, integrase cleaves two nucleotides from each 3' end of the linear double-stranded viral DNA, exposing hydroxyl groups; and (2) strand transfer — in the nucleus, integrase performs a concerted cleavage-ligation reaction inserting the processed viral DNA ends into the host chromosome by a cut-and-paste mechanism. INSTIs (raltegravir, elvitegravir, dolutegravir, bictegravir) specifically block the strand transfer step by chelating Mg2+ at the integrase active site. Reverse transcription is performed by reverse transcriptase; Gag-Pol cleavage is performed by HIV protease.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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