When HIV spreads to a new person, it infects their immune cells. This process — called the virus’s life cycle or replication cycle — has many steps, including entering a cell, making new virus copies, and exiting the cell.
Knowing more about how the virus works inside cells helps doctors and researchers better understand how to prevent and treat HIV infections.
The human immunodeficiency virus is a type of retrovirus. To better understand this and other virus types, it helps to learn about how genes work within viruses.
Like cells, viruses contain genes. Genes provide instructions that help viruses work properly. They allow a virus to make new copies of itself and spread. However, genes often work differently in viruses than they do in cells.
Human cells accomplish tasks using three main steps:
Viruses contain some of these components as cells. They generally have either DNA or RNA. They also contain proteins that allow the virus to function. For example, some proteins form the outer layer of the virus.
Some viruses store their genes in the form of DNA. The viruses that cause conditions like herpes and hepatitis B belong in this category. These viruses work similarly to human cells — they make RNA copies of their genes and use the RNA to make proteins.
Other viruses contain only RNA. These viruses cause diseases like influenza (the flu), measles, hepatitis C, and COVID-19. The process of storing genes and making proteins works differently in these viruses.
Retroviruses like HIV are types of RNA viruses. They work somewhat backward compared to DNA-containing cells and viruses. Instead of making RNA from DNA, they store all of their genes in the form of RNA. When retroviruses infect a cell, they use a special process called reverse transcription to make DNA copies of their RNA genes. The DNA copies are then embedded into the host cell’s DNA.
Human cells infected with retroviruses contain both the cell’s normal DNA and the virus DNA. When the cell makes RNA and proteins from its own DNA, it also produces virus RNA and protein. As a result, the virus can create more copies of itself.
When a person becomes infected with HIV and new virus particles are created, the virus can be found in the person’s blood, semen, breast milk, or fluid from the vagina or rectum. When a person without HIV comes into contact with these fluids, they may be exposed to the virus and could develop an infection.
HIV most often spreads during unprotected sex, while sharing needles or other drug-related equipment, during pregnancy, or while breastfeeding.
The steps of the HIV life cycle include entering a cell, making DNA and inserting it into the cell’s DNA, and forming new virus particles that leave the cell to infect additional cells.
HIV infects specific immune cells called CD4-positive T cells or T lymphocytes. These white blood cells help fight infection and kill germs. Many steps of the HIV life cycle harm the T cells, causing them to die. Fewer immune cells mean that people with HIV have a weakened immune system and are more likely to get infections.
Researchers have studied HIV’s life cycle to learn more about the virus. Using that knowledge, they have developed many different antiretroviral drugs that can block parts of this cycle and treat HIV.
The first step of an HIV infection happens when virus particles enter the body. Once inside, they eventually come into contact with T cells. Proteins on the virus bind (attach) to proteins on the cell.
A couple of different types of HIV medications block this step of the process and stop HIV from binding to T cells. They include:
After the binding step, an HIV particle and a T cell become attached. The next step occurs when the two fuse together.
Both the virus particle and the T cell have an outer layer. The virus’s outer covering is called the envelope, and the cell’s outer layer is called the cell membrane. During the fusion step of infection, these two layers join together. The envelope becomes part of the cell membrane, and all of the inner contents of the virus spill into the cell.
Fusion inhibitors such as enfuvirtide (Fuzeon) stop the envelope from fusing with the cell membrane.
Reverse transcription is the process of the virus’s RNA changing into DNA. One of the virus’s proteins (called reverse transcriptase) makes a copy of the viral RNA using DNA. The T cell then carries this viral DNA into the infected cell’s nucleus, where all the rest of the cell’s DNA is stored.
After this step, viral DNA is located in the same place as the cell’s DNA.
Several medications block this part of the HIV life cycle. These drugs prevent reverse transcriptase from creating virus DNA. These medications include both nucleoside reverse transcriptase inhibitors (NRTIs for short) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) like:
Once virus DNA has been created and moved into the cell’s nucleus, other virus proteins integrate (combine) this DNA with the cell’s DNA. The proteins make a cut in the cell’s DNA, insert the virus DNA, and attach all of the DNA together.
Once integration is complete, the virus DNA, which contains instructions for making new virus particles, is located in the middle of the cell’s DNA.
Integrase inhibitors are medications that block the integration step. These drugs include:
At this step in the life cycle, the infected T cell contains virus DNA within its own DNA. The virus DNA gives the cell instructions for making all of the different components used to make new viruses.
HIV uses the cell’s proteins and other materials to form an HIV factory, churning out virus building blocks including RNA and proteins. This is known as replication or transcription.
Once the cell has made the necessary building blocks for new HIV particles, all the pieces are assembled. Virus genetic material (in the form of RNA) and virus proteins group in one area near the cell’s outer membrane. They begin coming together to form an immature virus particle.
As thousands of viral proteins come together, they start to push their way out of the cell, creating a bulge on the cell’s surface. This is called budding. The virus particle eventually pushes its way out of the cell, forming an outer envelope made from viral proteins as well as pieces of the cell’s membrane.
After the virus particle breaks free from the cell, a protein called protease goes to work. It processes other virus proteins by taking long protein chains and cutting them into smaller pieces. These go on to perform different roles within the virus. This step, sometimes called maturation, results in a mature virus that is ready to infect other T cells. Once many T cells are infected, the immune system is unable to work as well as it should.
Protease inhibitors are HIV treatments that block the protease protein and prevent mature, working virus particles from forming. Protease inhibitors include:
If you’d like to understand HIV better, talk to your health care team. Ask your doctor for recommendations on reading materials or other resources that can help you better understand and manage your condition.
On myHIVteam — the social network for people with HIV and their loved ones — more than 35,000 members come together to ask questions, give advice, and share their stories with others who understand life with HIV.
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