Item 2 of 2
The patient is hospitalized, and appropriate treatment is begun. After discussing the underlying cause of his condition—immunosuppression due to HIV infection—the patient agrees to take antiretroviral therapy consistently. One of the medications in his treatment regimen leads to the production of immature, noninfectious virions containing large polyproteins. Which of the following viral processes is most likely directly inhibited by this agent?
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The HIV genome contains 3 major genes (env, gag, and pol) that are transcribed as polycistronic mRNA and translated into polyproteins in the endoplasmic reticulum. The gag and pol polyprotein products (gag-pol) are cleaved by HIV protease into individual HIV enzymes and structural proteins.
Protease inhibitors inhibit HIV protease from cleaving the gag-pol polyproteins, which results in the formation of immature, noninfectious virions due to impaired production of functional viral proteins. Protease inhibitors are a common component of first-line HIV antiretroviral therapy and are denoted by medications that end in "navir" (eg, darunavir, atazanavir, ritonavir).
(Choice A) The HIV envelope proteins gp120 and gp41 mediate viral attachment and fusion with the host cell membrane. These proteins are generated as a polyprotein (gp160) from the env gene. Unlike the gag-pol polyprotein (which is cleaved by HIV protease) the env polyprotein is cleaved by a host protease, so production of glycosylated viral envelope proteins is not affected by HIV protease inhibitors.
(Choices B and D) The pol gene encodes the major HIV enzymes: reverse transcriptase (RT), integrase, and protease. RT converts the HIV RNA genome into complementary double-stranded DNA; it also destroys the HIV RNA genomic template during transcription (ribonuclease H activity). RT is inhibited by nucleoside/nonnucleoside reverse transcriptase inhibitors. Integrase inserts complementary viral DNA into the host chromosome. Integrase strand transfer inhibitors block the function of this enzyme. Both RT and integrase inhibitors block viral replication, but neither are associated with immature virions containing polyproteins.
(Choice E) The HIV genome encodes for several regulatory proteins that are required for viral replication. However, all virus-encoded proteins are translated by host ribosomes, and blockade of protein translation would not be associated with the formation of polyproteins.
Educational objective:
The HIV genome contains 3 major structural genes that are translated as polyproteins and subsequently cleaved by host protease (env gene products) or viral protease (gag-pol gene products) into the individual proteins that compose the HIV virus. Protease inhibitors block viral protease from cleaving gag-pol polyproteins, which results in the formation of immature virions that are noninfectious.