Resistant to HIV infection: what makes it?

For a person to get an infection with HIV, they must have acquired the virus from external sources, the only external source is another human being infected with HIV. That human being can be his/her sexual partner or partner who shares injecting drug needles. People can also get an infection with HIV during birth via the birth canal, during breastfeeding, or via blood transfusion/organ transplant.

HIV and its receptors
Image Source: aids.info.nih.gov

But all people who are exposed to HIV virus do not get infected. Some people are Lucky!

Coreceptor is a protein on the surface of a cell that serves as a second binding site for a virus or other molecule. In order to enter a host cell, HIV must bind to two sites on the cell: the primary CD4 receptor and either the CCR5 or CXCR4 coreceptor.

Wondering how luck can protect from HIV Infection? or thinking these people might have used some preventive measures such as the use of condoms or screening of blood/organ, not sharing needles, etc! I am not talking about those preventive measures but their genetic makeup, making them resistant to HIV infection.

Each virus follows the same sequential steps during the infection process: attachment, penetration and uncoating, replication and biosynthesis, assembly, and release. So the very first and crucial step is the attachment of the virus to its (specific) host cells. One good news for humans is that viruses are very specific regarding their attachment to host cells.

Whenever we try to climb trees or very steep slopes (mountains), we need something to assist us in adhering there. That may be a rope or branch of a tree or rough surface. Can you imagine successfully climbing mountains, hills, or trees if these things are unavailable? It is impossible! Similarly, for the virus to attach to the host cell, they need “something (like rope or branch of a tree)” which helps them to make a firm grip. That “something” is a receptor.

To enter a CD4 cell, HIV must first attach to a CD4 receptor, attach to the CCR5 or CXCR4 coreceptor, and finally fuse its membrane with the CD4 cell membrane. HIV can attach only to those CD4 cells which have specific chemokine receptors CXCR4 and/or CCR5. HIV is usually R5-tropic (uses CCR5) during the early stages of infection, but the virus may later switch to using either only CXCR4 (X4-tropic) or both CCR5 and CXCR4 (dual-tropic). If a particular CD4 cell lacks CCR5 or CXCR4 coreceptor, then the HIV can not attach to these CD4 cells, so the HIV infection/replication process is halted before it can start.

A new class of antiretroviral drugs used in treating human immunodeficiency virus (HIV), called CCR5 inhibitors, is designed to prevent HIV infection of CD4 T-cells by blocking the CCR5 receptor.

Image Source: aids.info.nih.gov

Studies have found that mutations in the gene encoding CCR5 endow individuals with protection from HIV infection. People who are homozygotes are entirely resistant to HIV infection, whereas, among heterozygotes, HIV infection progresses very slowly.

Some of these lucky HIV-resistant people live in Western Europe (Who knows, many people in your country might also be resistant to HIV!). Approximately 1% of people of western European ancestry have homozygous mutations in their gene, and about 10-15% are heterozygotes.

Do you know?

Timothy Ray Brown- The Berlin Patient is the first person to be cured of AIDS.

Timothy Brown
Timothy Ray Brown-First patient cured of HIV/AIDS

Timothy Brown, famously known as “The Berlin Patient,” is thought to be the first and only individual functionally cured of HIV. He was diagnosed with HIV in 1995, and a decade later, he was diagnosed with acute myeloid leukemia.  He received a bone marrow transplant (with a mutation on the CCR5-delta32 gene).

Brown received two stem cell transplants that knocked out his cancer as well as HIV.  He founded Timothy Ray Brown Foundation in Washington, DC, a foundation dedicated to fighting HIV/AIDS.

Read more about fascinating cases of two people who have effectively vanquished HIV in the book Cured: The People Who Defeated HIV

You can watch an interview with Timothy Brown here

References: 

  1. Samson, M., Libert, F., Doranz, B. J., Rucker, J., Liesnard, C., Farber, C. M., Saragosti, S., Lapoumeroulie, C., Cognaux, J., Forceille, C., Muyldermans, G., Verhofstede, C., Burtonboy, G., Georges, M., Imai, T., Rana, S., Yi, Y., Smyth, R. J., Collman, R. G., Doms, R. W., … Parmentier, M. (1996). Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature, 382(6593), 722–725. https://doi.org/10.1038/382722a0
  2. Biasin, M., De Luca, M., Gnudi, F., & Clerici, M. (2013). The genetic basis of resistance to HIV infection and disease progression. Expert review of clinical immunology, 9(4), 319–334. https://doi.org/10.1586/eci.13.16
  3. Marmor, M., Hertzmark, K., Thomas, S. M., Halkitis, P. N., & Vogler, M. (2006). Resistance to HIV infection. Journal of urban health : bulletin of the New York Academy of Medicine, 83(1), 5–17. https://doi.org/10.1007/s11524-005-9003-8

Acharya Tankeshwar

Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion. As an asst. professor, I am teaching microbiology and immunology to medical and nursing students at PAHS, Nepal. I have been working as a microbiologist at Patan hospital for more than 10 years.

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