Characteristics of HIV and its life cycle
The human immunodeficiency virus belongs to retroviruses and contains RNA. For successful pharmacotherapy, it is important to consider all stages of its replication, of which there are eight. The virus life cycle begins with adsorption, where glycoprotein gp120 and CD4 receptors with the CCR5 co-receptor are responsible for attachment to the target cell surface. This is followed by penetration—fusion of the virion envelope with the cell membrane.
Inside the cell, reverse transcription takes place, during which double-stranded DNA (provirus) is synthesized on the viral RNA template. This process is catalyzed by the enzyme reverse transcriptase. The synthesized DNA enters the host cell nucleus, where integrase ensures its integration into the human genome. The integrated provirus can remain inactive for years, creating a risk of relapses.
Protein synthesis and virus maturation
Following integration, the genetic information of the virus is realized through the transcription of proviral DNA into mRNA and the synthesis of new viral RNAs. mRNA translation into viral precursor proteins occurs on the cell ribosomes. The provirus encodes three critical groups of proteins:
- Enzymes: reverse transcriptase, integrase, and protease.
- Polypeptide precursors: long polypeptide chains.
- Transmembrane protein (gp160): penetrates the lipid envelope and is responsible for cell penetration.
At the final stage of assembly and exit, a viral particle is formed. During maturation, the viral protease cleaves long polypeptide chains into individual functional proteins, making the new virion infectious.
Sites of action of antiretroviral drugs
Pharmacological action aims to block key steps of virus replication. Main targets include viral enzymes and the cell entry process:
- Early stages: blockade of the CCR5 co-receptor (Maraviroc) and inhibition of the fusion process (Enfuvirtide).
- Genetic material synthesis: inhibition of reverse transcriptase (Zidovudine) and integrase (Raltegravir).
- Late stages and maturation: inhibition of HIV protease (Indinavir, Ritonavir).
Widely used drug classes are represented by modified nucleosides and nucleotides with altered structures, as well as non-nucleoside reverse transcriptase inhibitors.
Briefly: answers to topical questions
Which drugs belong to HIV protease inhibitors?
The group of HIV protease inhibitors includes such drugs as saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, darunavir, and fosamprenavir. Combination forms including a combination of lopinavir and ritonavir are also used. These medicinal products act at the late stage of viral replication and prevent viral mRNA maturation.
- Saquinavir is the first representative of the protease inhibitor group.
- Ritonavir is a drug also used as a pharmacokinetic enhancer.
- Lopinavir is part of combination forms with ritonavir.
Which receptors and co-ceptors are involved in the HIV adsorption stage?
During the HIV adsorption stage, the virus attaches to the target cell surface using key structural components. This process involves the viral glycoprotein gp120 and specific cellular receptors and co-receptors.
- CD4 is the main host cell receptor.
- CCR5 is a chemokine co-receptor.
- CXCR4 is a chemokine co-receptor.
Which drugs belong to the group of nucleoside reverse transcriptase inhibitors?
The group of nucleoside reverse transcriptase inhibitors includes drugs that are analogues of natural nucleosides and nucleotides with an altered structure. They prevent the synthesis of viral DNA at the early stage of viral replication.
- Zidovudine is a thymidine analogue used in treatment regimens.
- Abacavir — a guanine analog.
- Lamivudine — a cytidine analog.
- Emtricitabine — a cytidine analog.
- Tenofovir — a nucleotide analog of adenine.
How do nucleoside reverse transcriptase inhibitors differ from non-nucleoside ones?
Differences between the reverse transcriptase inhibitor groups lie in their chemical structure and the mechanism of interaction with the reverse transcriptase enzyme. Nucleoside inhibitors are abnormal analogues of natural nucleosides.
| Parameter | Nucleoside inhibitors (NRTIs) | Non-nucleoside inhibitors (NNRTIs) |
|---|---|---|
| Structure | Altered structure (nucleoside and nucleotide analogues) | Not specified in sources as a detailed comparison |
| Mechanism | Incorporate into the synthesized viral DNA chain and cause chain termination | Not detailed in the context of this comparison in the text |
What side effects are characteristic of zidovudine?
Zidovudine is characterized by a number of serious side effects and toxicity manifestations that require mandatory monitoring of the patient's condition.
- Hematological disorders (myelosuppression) — suppression of hematopoiesis manifesting as anemia, neutropenia, leukopenia, and thrombocytopenia.
- Mitochondrial toxicity — suppression of mitochondrial DNA synthesis causing myopathy.
- Hepatotoxicity — possible development of hepatic steatosis and acidosis.
- Neurotoxic and general reactions — headache, insomnia, agitation, paresthesia, dyspeptic disorders, skin rash, and fever.
The order of action of viral enzymes is easy to remember by the acronym "RIP": Reverse transcriptase builds DNA, Integrase inserts it into the genome, and Protease cleaves proteins for maturation.
Class and exam questions
Which virus family does HIV belong to?
The human immunodeficiency virus belongs to the retrovirus family and is an RNA-containing virus.
What role does reverse transcriptase play?
Reverse transcriptase (RNA-dependent DNA polymerase) ensures the process of reverse transcription — the synthesis of double-stranded DNA (provirus) on a viral RNA template.
What groups of proteins does proviral DNA encode?
The provirus encodes three groups of proteins: enzymes (reverse transcriptase, integrase, protease), polypeptide precursors, and the transmembrane protein gp160.
What are the targets of Maraviroc and Raltegravir?
Maraviroc blocks the CCR5 co-receptor at the virus adsorption stage, and Raltegravir inhibits integrase at the stage of viral DNA insertion into the host genome.
What else to study on this topic
- Features of herpes virus resistance and thymidine kinase deficiency
- Detailed mechanism of reverse transcription and provirus synthesis
- Role of transmembrane proteins gp120 and gp41 in adsorption and fusion
- Structure and functions of viral polypeptide precursors
- Differences between nucleoside and non-nucleoside reverse transcriptase inhibitors
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