How Human Immunodeficiency Virus Replicates in the Body

My STEAM project depicts how HIV replicates in the body. 

This relates to the objectives: 

29. Explain the role of the lymphatic system in the immune response 

30. Identify the key structures of the lymphatic system

31. Relate how the lymphatic system can indicate disease

Human Immunodeficiency Virus or HIV appeared in humans from chimpanzees in Central Africa as far back as the 1800s and spread to the United States in the 1970s(1). HIV is an exogenous retrovirus that attacks the immune system, meaning it originates from outside the body and makes copies of DNA to insert into the host cell nucleus, which then produces more of the virus that goes on to infect more white blood cells. HIV is transmitted by contact with infected bodily fluids such as blood, semen, vaginal and anal secretions, and breast milk. After infection occurs, often through sexual intercourse, HIV begins to multiply in the mucosal tissue and within a few days the virus spreads into the lymphoid tissue which causes swelling of lymph nodes. In roughly 10 days HIV is detectable in the bloodstream growing rampantly until it peaks after about 30 days(5). HIV has 3 stages starting with an acute HIV infection with symptoms like the flu. The chronic HIV infection stage is latent and can be asymptomatic but can last for a decade or more and still transmit the virus. The third stage is Acquired Immunodeficiency Syndrome or AIDS where the virus has proliferated and is easily transmissible. AIDS severely weakens the immune system and the body is not as capable of fighting infections (1). Antiretroviral therapy (ART) is used to inhibit the production of HIV at the cellular level. With ART, levels of HIV can be undetectable, where the virus cannot be transmitted.   

The virus has an external lipid bilayer of glycoproteins that attach to the CD 4 receptor on macrophages and T lymphocytes and will enter through endocytosis if the CCR 5 coreceptor is also present. Once inside the cell, the reverse transcriptase enzyme transcribes its viral RNA to DNA and merges with the leukocytes’ DNA. Transcription of the cell’s DNA now carries viral messenger RNA that produces the virus and exits the cell through exocytosis. This process keeps the cell alive while reproducing more of the virus. The virus mutates glycoprotein 120 to change its coreceptor to CXCR 4 which is also found on T cells (3, 8). However, as this form of the virus replicates and exits through the plasma membrane, the membrane ruptures and kills the cell. Destruction of these cells leads to a weakened immune system and the onset of AIDS leaves the person vulnerable to opportunistic infections that occur more frequently and are more severe. 

While there is no cure for HIV, antiretroviral therapy uses medications to inhibit HIV replication and decrease viral load which prevents HIV from progressing to AIDS. There are 5 unique classes of antiretroviral drugs that target a different stage of HIV replication. Entry inhibitors prevent the R5 variant virus from attaching to CCR 5 receptors. Nucleoside reverse transcriptase inhibitors (NRTIs) use decoy nucleosides to prevent transcription while non-nucleoside reverse transcriptase inhibitors (NNRTIs) attach to reverse transcriptase to block transcription. Capsid inhibitors prevent the virus from entering the nucleus while integrase strand transfer inhibitors (INSTIs) attach to integrase to prevent the virus from inserting its DNA. Protease inhibitors block the use of proteins that make more of the virus. These medications are paired with pharmacokinetic enhancers that slow the breakdown of other medications allowing them more time to work (4,5). Antiretroviral therapy can reduce HIV to undetectable levels but medication has to be taken regularly for the rest of their lives. 

1. About HIV/AIDS. Centers for Disease Control and Prevention. (2022, June 30). https://www.cdc.gov/hiv/basics/whatishiv.html 
2. Aids and Opportunistic Infections. Centers for Disease Control and Prevention. (2021, May 20). https://www.cdc.gov/hiv/basics/livingwithhiv/opportunisticinfections.html 
3. Cloyd, M. W. (1996). Human retroviruses. U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK7934/ 
4. Antiretroviral therapy. Cleveland Clinic. (2023, September 18). https://my.clevelandclinic.org/health/treatments/antiretroviral-therapy
5. Deeks, S. G., Overbaugh, J., Phillips, A., & Buchbinder, S. (2015, October 1). HIV infection. Nature Reviews Disease Primers. https://www.nature.com/articles/nrdp201535 
6. Garcia, S. A. B. (2023, August 14). Acquired immune deficiency syndrome CD4+ count. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK513289/ 
7. Soares, H. (2014, September 22). HIV-1 intersection with CD4 T cell vesicle exocytosis: Intercellular communication goes viral. U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170133/#:~:text=Seemingly%2C%20HIV%2D1%20hijacks%20the,exocytosis%20is%20the%20immunological%20synapse. 
8. Spach, D. H., & Wood, B. R. (2023, November 3). Antiretroviral Medications and Initial Therapy. National HIV Curriculum. https://www.hiv.uw.edu/go/antiretroviral-therapy/general-information/core-concept/all