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How Does It Work?
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| How does HIV work? |
How does HIV work?1-6
Viral infections occur when viruses attach to and penetrate cells. Viruses target specific cell types, which are identified and distinguished by the proteins located on the surface of the cell – different cells display different proteins, which are attractive to different viruses.
In the case of human immunodeficiency virus (HIV), T-cells and macrophages are the main cell types targeted by the virus. T-cells and macrophages are key players in the human immune system. The immune system is the body’s defense against all kinds of infections (e.g., viral, bacterial, or fungal), foreign bodies (e.g., pollen and other allergens), and other factors that cause disease. The destruction of the immune system is particularly devastating, as it renders the person unable to fight off infectious and non-communicable (or non-infectious) diseases. For example, HIV/AIDS initially garnered attention in the early 1980s when clusters of young gay men developed unusual diseases such as Kaposi sarcoma and Pneumocystis carinii pneumonia, which were unusual for this population.
The HIV Virus7 Courtesy: The National Institute of Allergy and Infectious Diseases | website
The course of HIV/AIDS is complex. The presence of antibodies indicates infection with HIV. T-cell counts (specifically those with CD4+ protein on their surface – T-helper cells) are useful in determining the severity of the infection and decisions about treatment. This measure is also used to diagnose AIDS. Viral load measures are used to assess the progression of the disease and whether treatment is working.
In the acute phase (first several weeks following infection), the person may experience mild fatigue and fever as the number of virus copies (viral load) in the blood increases. The high viral load increases the person’s ability to infect someone else, particularly as the person does not appear seriously ill. High viral load is important for transmission because HIV is considerably less infective than many other viruses, including other sexually transmitted infections. Viral load tests can detect the virus about 2 weeks after infection. During this period, the number of T-helper cells in the blood decreases, T-cells with CD8 protein (T-cytotoxic cells) increase, and antibodies to the virus are produced.
During the asymptomatic phase (months or years after infection), both the viral load and the risk of transmission are decreased. At the same time, T-helper cells increase and antibodies and T-cytotoxic cells level off. Within one to three months, antibodies become detectable in the blood. This phase may last for many years, though most people start to experience symptoms within 10 years.
In the final phase (AIDS), viral load increases as copies of the virus are released into the blood and CD4+ T-cells decrease as these cells are destroyed. At this point, most infected people develop symptoms of the disease, including weight loss and fever. The transition from “living with HIV” to a diagnosis of AIDS occurs when the CD4+ count drops from a normal range of 500 – 1500 cells per cubic millimeter to less than 200 cells/mm3 or when the CD4+ cells are only 14 percent of total lymphocytes (B-cells + T-cells).
The Course of HIV Infection and AIDS4 Reprinted from The Lancet, vol. 368, Viviana Simon, David D Ho, Quarraisha Abdool Karim,
HIV epidemiology, pathogenesis, prevention, and treatment, 489-504, Copyright (2006),
with permission from Elsevie | website
HIV targets T-helper cells, using them to produce new copies of the virus. These cells play a crucial role in coordinating the immune system’s response to infection and stimulating production of immune system cells (T-cytotoxic and B-cells).
- T-helper cells stimulate production of T-cytotoxic cells that ingest and destroy all types of viruses.
- T-helper cells stimulate production of B-cells, which produce antibodies, and then they help the B-cells ingest and eliminate viruses.
HIV binds to the T-helper cell’s CD4+ protein and co-receptor, which are located on the surface of the T-cell. Once the virus attaches to these proteins, it can enter the cell. Once inside the cell, the virus disassembles, uses the cell’s own machinery to produce viral proteins, and reassembles. When the new viruses exit the T-helper cell, most (but not all) host cells are killed – ruptured as the virus is released.
In addition to the T-helper cells, HIV targets macrophages and T-memory cells. These cells and some T-helper cells are infected with but not killed by HIV. These cells harbor viral particles, which use the cells to generate more viruses that are dispersed to infect other cells – in effect, becoming virus producing factories.
- Macrophages engulf foreign substances and microbes, and are part of the immune system’s first line of defense against infection. Generally, the engulfed substance is destroyed, but HIV lodges in the cell and may remain dormant for several years.
- T-memory cells “remember” past infections, resulting in a more rapid response if a foreign body, such as a virus or bacteria, is reintroduced into the body. As with macrophages, T-memory cells harbor HIV particles and then become factories for producing copies of the virus.
- This process allows for the “latent” or asymptomatic state of infection, in which copies of the virus infect cells but the viral load in the blood is at undetectably low levels. This asymptomatic phase can last for several years.
HIV, like other viruses, is able to mutate.4 In particular, the proteins on HIV’s viral envelope (outside coat) have a high mutation rate and can even mutate over time within an individual. These mutations make it easier for the virus to evade the immune system, as differences in the surface proteins make the virus harder to identify. Similarly, development of vaccines or medications that target HIV may be less effective (or ineffective) against strains of the virus with different viral envelope proteins.
There are two strains of HIV: HIV-1 and HIV-2. HIV-1 is by far the most prominent strain, with HIV-2 found in some West African countries. HIV-2 appears to be less efficient than HIV-1 in causing AIDS and is harder to detect with current tests. HIV-1 is composed of three groups: M, N, and O. Group M is the predominant group, and it is composed of nine subtypes.
The predominant subtype is C, which is responsible for more than half of infections
worldwide.4, 8 It is possible for people to be infected by more than one subtype, which may result in a newly formed “recombinant” form of the virus and greater complexity in treating the disease. It is likely that HIV-1 originated in Central Africa, as this region houses all nine subtypes in group M and groups N and O.
| Subtype |
Prominent in Region |
| A |
Sub-Saharan Africa, Eastern Europe and Central Asia |
| B |
North America, Latin America, Caribbean, Europe (all), Asia (all), Oceania, North Africa and Middle East |
| C |
East Asia, Sub-Saharan Africa, North Africa and Middle East |
| D, F, G, H, J, K |
Sub-Saharan Africa |
* On our website, HIV refers to HIV-1.
| 1 |
Fan HY, Conner RF, Villareal LP. 2004. AIDS science and society. 4th ed. Boston: Jones and Bartlett Publishers. |
| 2 |
National Institute of Allergy and Infectious Disease. 2003. Understanding the immune system: how it works. Available from: www3.niaid.nih.gov/healthscience/healthtopics/immuneSystem/PDF/theImmuneSystem.pdf |
| 3 |
Chin J. 2007. The AIDS Pandemic: the collision of epidemiology with political correctness. Oxford: Radcliffe Publishing. |
| 4 |
Simon V, Ho DD, Karim QA. 2006. HIV/AIDS epidemiology, pathogenesis, prevention, and treatment. Lancet 368:489-504. |
| 5 |
Prendergast A, Tudor-Williams G, Burchett S, Goulder P. 2007. International perspectives, progress, and future challenges of paediatric HIV infection. Lancet 370:68-80. |
| 6 |
Heymann DL, editor. Control of communicable diseases manual. 18 ed. Washington, DC: American Public Health Association, 2004. |
| 7 |
National Institute of Allergy and Infectious Disease. How HIV causes AIDS. (accessed October 31, 2007), Available from: www.niaid.nih.gov/factsheets/howhiv.htm |
| 8 |
Avert. Introduction to HIV types, groups and subtypes. (accessed February 19, 2008), Available from: www.avert.org/hivtypes.htm |
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