22nd International AIDS Conference
Amsterdam, Netherlands | 23-27 July 2018

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The life cycle of HIV

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HIV belongs to a class of viruses that are called Retroviruses. Retroviruses, like all other viruses, need a host cell to produce and replicate their own DNA to make more viruses. HIV replication is a complex process with several stages. These stages are called Attachment, Fusion, Reverse Transcription, Integration, Replication, Assembly and Maturation.

In order to understand the HIV replication process, first we need to look into structure of HIV. HIV is a round ball shaped virus. The outer layer of this ball is called the envelope and on the envelope there are spike like protein complexes called glycoprotein 120 (gp120) and glycoprotein 41 (gp41). In the envelope there is the HIV capsid. It contains two single strands of RNA (which carry the genetic code of the virus) and 3 enzymes (Integrase, Protease and Reverse Transcriptase). 1

Attachment and fusion

The replication process starts with the infection of a host cell. HIV targets CD4 t-cells as host cells. It uses CCR5 receptors and CXCR4 co-receptors on the CD4 host cell to bind itself to the surface of the CD4 cell. The gp120 helps the virus to attach itself to the CD4 receptors. Then the gp41 helps the HIV envelope to fuse itself with CD4 membrane and enter the CD4 cell. This fusion finalizes the first two stages in the HIV replication which are called attachment and fusion.2

Reverse transcriptase

After the attachment and fusion is complete, the HIV capsid breaks open in the CD4 cell and releases the strands of RNA as well as the replication enzymes. The first thing HIV needs to do, is to convert its single stranded RNA to double helix DNA, because RNA cannot be copied by the host cell. Normally DNA is converted to RNA with a process called transcriptase. However, HIV does it the other way around, with the help of the reverse transcriptase enzyme. This is why this class of viruses are called Retroviruses.2

Integration

After HIV has its own DNA in the CD4 cell it is not attached to anything. This produced DNA now needs to be integrated into the host cell’s DNA. This is where the second enzyme called Integrase steps in. It cuts small pieces from each end of the viral DNA strands and binds these ends to the host cell’s DNA.

Replication

After the Integration stage is completed viral DNA is part of the host cell’s DNA. This means every the time the host cell replicates its own DNA it also replicates the viral DNA. HIV does not only use the CD4 cell to reproduce its DNA but also to build long chains of proteins, which will be used as building blocks for more HIV. 3

Assembly

These long chains of proteins will be cut into to short pieces of proteins with the help of third enzyme called Protease. At this stage of the life cycle, HIV has produced the necessary proteins to build more HIV particles. These proteins together with two strands of RNA and the replication enzymes will start gathering on the surface of CD4 cell and they will start forming a new HIV capsid.

Maturation

After the Assembly stage, this newly formed HIV capsid will be pushed out of the CD4 cell. While leaving the CD4 cell the HIV capsid will form a new envelope from the CD4 surface and viral proteins. Outside the host cell this new HIV particle matures until it becomes infectious enough to target other CD4 cells.4

Understanding this replication process is important, because when HIV is left untreated it keeps replicating itself, destroying CD4 cells and damaging the immune system. With modern treatment, each of these replication stages can be targeted with different classes of HIV drugs and progress of HIV can be stopped by preventing CD4 cells from being damaged and protecting the immune system from weakening.


Footnotes

1 https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/73/the-hiv-life-cycle

2 https://study.com/academy/lesson/hiv-virus-structure-and-function.html

3 https://www.youtube.com/watch?v=RO8MP3wMvqg

4 https://www.niaid.nih.gov/diseases-conditions/hiv-replication-cycle

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