What is the life cycle of HIV? Target stages of antiretroviral drugs

HIV (human immunodeficiency virus) is an infection that affects approximately 1.2 million people in the United States.

The infection is very difficult to treat because the virus combines its genetic information with the genetic information of a type of white blood cell called CD4 cells. HIV can continue to replicate without treatment, generating more than 10 billion new virus particles per day.

HIV has three main stages:

  • Acute HIV. There is a lot of HIV in your blood. Some people develop flu-like symptoms like chills, fever, and sore throat. It occurs about 2 to 4 weeks after exposure.
  • Chronic HIV. After the acute symptoms subside, you enter the chronic phase where HIV replicates at low levels. You are still contagious at this stage, but you may not have any symptoms.
  • AIDS. AIDS is the last stage of HIV and severely damages your immune system. It is characterized by a CD4 count of less than 200 cells per cubic millimeter of blood.

The replication cycle, or life cycle, of HIV can be divided into seven stages. Medicines that treat HIV interrupt one of the seven stages of the HIV life cycle.

In an actively infected cell, the complete life cycle lasts only 1 or 2 days. But some cells can become latently infected, which means that HIV can potentially be present in them for years without producing new virus particles. At any time, these cells can activate and start making viruses.

In this article, we describe what happens during each of the seven stages of the HIV life cycle and how drugs disrupt these processes.

HIV belongs to a group of viruses called retroviruses. These viruses are difficult to get rid of because they integrate with the host cell’s DNA as part of their life cycle.

During the first stage of the HIV life cycle, the virus binds to receptors on the surface of CD4 cells. CD4 cells, also called helper T cells, are a type of white blood cell that alerts other immune cells to the presence of infection in your body.

HIV is an enveloped virus, which means that its genetic information is protected by both a protein envelope and a lipid layer called an envelope.

Once HIV binds to CD4 cell receptors, it initiates the fusion of its envelope with the CD4 cell membrane using a glycoprotein called GP120. Glycoproteins are molecules made up of chains of carbohydrates and proteins.

Fusion with the membrane of your CD4 cells allows the virus to enter the cell.

Reverse transcription is the process of converting genetic information in the form of RNA into DNA. RNA and DNA contain similar genetic information but are structurally different. RNA is usually made up of a long chain of genetic information, while DNA is made up of a double strand.

The virus converts its RNA into DNA by releasing an enzyme called reverse transcriptase. This process allows the virus’s genetic information to enter the nucleus of your CD4 cell.

After HIV converts its RNA into DNA, it then releases another enzyme called integrase inside the nucleus of your CD4 cell. The virus uses this enzyme to combine its DNA into the DNA of your CD4 cell.

At this point, the infection is still considered latent and is difficult to detect even with sensitive lab tests.

Because HIV is now integrated into the DNA of your CD4 cell, it can use that cell’s machinery to generate viral proteins. During this time, it can also produce more of its genetic material (RNA). These two things allow it to create more virus particles.

At the assembly stage, new HIV proteins and RNA are sent to the periphery of your CD4 cell and become immature HIV. These viruses are non-infectious in their present form.

During the budding phase, immature viruses push out of your CD4 cell. They then release an enzyme called a protease which changes the proteins of the virus and creates a mature, infectious version.

The main goals of antiretroviral therapy are to stop HIV from replicating itself and to suppress your viral load to a point where it is no longer detectable.

Antiretroviral drugs are divided into seven classes of drugs depending on which part of the HIV life cycle they interrupt. At least two different classes of drugs are used during antiretroviral therapy. Each drug usually contains two or three drugs.

Antivirals at the binding stage

CCR5 antagonists

CCR5 antagonists block the CCR5 coreceptor on the surface of your CD4 cells to disrupt the binding phase. CCR5 is the main co-receptor used by the GP120 glycoprotein on the surface of HIV to enter your cells.

A coreceptor is a special type of receptor required by the virus to enter a cell.

Post-attachment inhibitors

Post-attachment inhibitors bind to receptors in CD4 cells. This activity prevents HIV from binding to two types of co-receptors called CCR5 and CXCR4 and prevents the virus from entering your CD4 cells during the binding phase.

Antivirals at the fusion stage

Fusion inhibitors

Fusion inhibitors block the ability of the HIV envelope to combine with the membrane of a CD4 cell. This action prevents the virus from entering your cells.

Antivirals at the reverse transcription stage

Nucleoside reverse transcriptase inhibitors (NRTIs)

NRTIs prevent HIV from using the enzyme reverse transcriptase to replicate. Reverse transcriptase allows the virus to convert its RNA into DNA at the reverse transcription stage of its life cycle. The drug prevents the virus from copying its RNA into DNA precisely.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

NNRTIs turn off a key protein that HIV uses to replicate. They work the same way as NRTIs by preventing the virus from replicating itself.

Antivirals in the integration phase

Integrase strand transfer inhibitors

Integrase strand transfer inhibitors block the integrase enzyme that HIV uses to combine its reverse transcribed DNA with the DNA in your cell during the integration phase.

Antivirals in the budding stage

Protease inhibitors

Protease inhibitors block the protease enzyme during the budding phase. Protease is an enzyme that allows immature HIV to develop into mature viruses that can infect other CD4 cells.

HIV replicates itself by combining its genetic information with the genetic information of your CD4 white blood cells.

The process of replication, or the life cycle of HIV, has seven stages.

Antiretroviral therapy includes drugs from at least two types of drug classes. Each class of drugs prevents the virus from replicating by inhibiting a particular part of the HIV life cycle.

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