How HIV Hijacks Humans and Destroys the Immune System

Written By Vaishnavi Kolluru

Human immunodeficiency virus (HIV) ruins the host immune system. An antigen presenting cell presents a HIV antigen to a helper T cell (TH). The following receptors are necessary for HIV envelope proteins to bind and for the particle to enter the TH cell: CD4, CCR5, and CXCR4 (least prevalent). The CD4 receptor is the main one, and the other two are coreceptors, since they facilitate binding. This causes a conformational change in the receptor, and the receptor-ligand complex bends, increasing HIV particle-host cell proximity. This facilitates membrane fusion, so the HIV particle injects its genetic material into the TH cell.

As HIV is a retrovirus (+RNA genome), it utilizes reverse transcriptase to turn its ssRNA genome into ssDNA, which is replicated to dsDNA, which is then integrated into the host genome via the integrase enzyme. However, as reverse transcriptase has faulty proofreading systems, HIV mutation is very likely, making vaccines (preventative) and antivirals (preventative, or can be designed to inhibit viral replication) ineffective.

^ Baltimore virus classification!

Integration of “viral DNA” into the host genome allows for synthesis of new HIV envelope proteins, which propagate the viral infection. Translated envelope proteins are inserted on the TH cell membrane. Additionally, integrase and reverse transcriptase are synthesized from viral genetic material. These accessory enzymes are complexed into polyproteins, which can be cleaved to activate the constituent proteins. These polyproteins are exocytosed with the envelope proteins around the vesicle membrane, effectively creating immature virus particles. Cleavage of the polyproteins by protease can cause the immature virus to become a mature virion.

The HIV life cycle damages T cells by various means. For example, immature viruses budding out of the TH cells initiates pyroptosis, which is cell death due to excessive inflammation. However, most of the TH cells that die in AIDS are uninfected. The inflammatory products that are released from a pyroptosed cell signal to surrounding cells to also pyroptose. (This is very similar to excitotoxicity of neurons!)

Death can also occur when integrase activity is detected since cells can detect when DNA is being broken by integrase before insertion. The self destruction is apoptosis in this case. Additionally, as vesicles are budding out of the TH cell, proteases need to cut the polyprotein. However, the proteases also cut a caspase and this causes apoptosis as well. (See this article to learn more about apoptosis.) Also, CD8 cells can kill infected CD4 cells. Finally, uninfected TH cells can get signaling from infected ones and produce defense proteins, and they travel to lymph nodes. In the lymph nodes, HIV exposure induces interleukin-1 expression, and this causes surrounding TH pyroptosis due to an inflammation cascade. The pro-inflammatory molecules spread this signal for pyroptosis.

These are the various ways that HIV beats the system.

To learn more, watch these videos:

Vaishnavi Kolluru
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