What is the Difference Between CCR5 and CXCR4

The main difference between CCR5 and CXCR4 is that CCR5 is important for viral entry during the early stages of HIV infection, whereas CXCR4 is important for viral entry during the later stages of HIV infection.

CCR5 and CXCR4 are two types of coreceptor proteins that occur in white blood cells. They are coreceptors for viral entry during HIV infection.  

Key Areas Covered

1. What is CCR5
– Definition, Features, Importance
2. What is CXCR4
– Definition, Features, Importance
3. Similarities Between CCR5 and CXCR4
– Outline of Common Features
4. Difference Between CCR5 and CXCR4
– Comparison of Key Differences

Key Terms

CCR5, CXCR4, CD184, CD 195, Chemokine Receptor Type 5, C-X-C Chemokine Receptor Type 4

What is CCR5

The CCR5 or chemokine receptor type 5 or CD 195 is a protein that expresses in white blood cells. They are a type of beta chemokine receptors. CCR5 predominantly expresses in macrophages, dendritic cells, T cells, eosinophils, and in microglia. Along with the CD4 receptors, CCR5 coreceptors allow the entry of the HIV-I virus. The envelope glycoprotein structure consists of two glycoproteins: Gp120 and Gp41. Here, Gp120 is an external subunit, while Gp41 is a transmembrane subunit. Gp120 can bind with the chemokine receptors such as CCR5. This binding forms a heterotrimeric complex. The formation of this complex stimulates the release of a fusogenic peptide that causes the viral membrane to fuse with the target host cell membrane.

Figure 1: CCR5

Furthermore, the expression of CCR5 receptors is selectively induced in breast and prostate epithelial cells during cancer formation. Approximately 50% of breast cancer induces the expression of CCR5 receptors. Therefore, CCR5 inhibitors can serve as a new therapeutic agent in cancer treatments. Also, CCR5 expresses in cancer stem cells, and CCR5 inhibitors enhance the number of cancer cells killed by chemotherapy.

What is CXCR4

CXCR4 or c-x-c chemokine receptor type 4 or CD184 is a chemokine receptor in the human body. HIV-I strains use CXCR4 as a coreceptor for the infection of CD4+ T cells. The types of cells infected by HIV-I strains are known as T-cell tropic isolates. Infection of these cells occurs in the late stages of the infection by HIV-I infection. Furthermore, CXCR4 is upregulated during the implantation window in nature. Also, it increases during hormone replacement therapy. Apart from that, SDF-1 is the ligand of the CXCR4 receptor. They are monogamous ligand-receptor pair. Besides, ubiquitin is also a ligand for the CXCR4 receptor.

Figure 2: CXCR4

Moreover, CXCR4 expresses in newly generated neurons during embryogenesis as well as in adults. It has a role in neuronal guidance. The levels of receptors reduce in number with the maturation of the neurons.

Similarities Between CCR5 and CXCR4

• CCR5 and CXCR4 are two types of coreceptors that occur on the surface of white blood cells.
• They are important for viral entry during HIV infection.
• They are a type of chemokine receptors that postulate the direct migration of leukocytes to the sites of inflammation.

Difference Between CCR5 and CXCR4

Definition

CCR5 refers to a chemokine receptor found on monocytes and lymphocytes that serves as the coreceptor for HIV, while CXCR4 refers to a receptor that acts with the CD4 protein to support HIV entry into cells.

Also Called

The CCR5 receptor is also known as CD195, while the CXCR4 receptor is also known as CD184.

HIV Viral Entry

CCR5 is important for viral entry during the early stages of HIV infection, while CXCR4 is important for viral entry during the later stages of HIV infection.

Type of Viral Strains

CCR5 promotes the entry of M-tropic HIV-1 strains, while CXCR4 promotes the entry of T-tropic HIV-1 strains.

Type of Cells

CCR5 coreceptors mainly express on macrophages, while CXCR4 coreceptors mainly express on T cells.

Viral Strains

R5-tropic viruses prefer CCR5 coreceptors, while X4-tropic viruses prefer CXCR4 coreceptors.

Conclusion

In brief, CCR5 and CXCR4 are two types of coreceptors important in the viral entry during HIV infection. The CCR5 receptor is also known as CD195, and it is important in the viral entry during the early stages of HIV infection. Also, it promotes the entry of M-tropic HIV-1 strains. In addition, CCR5 coreceptors are preferred by R5-tropic viruses. In comparison, CXCR4 or CD184 coreceptor is important in the viral entry of the later stages of the viral entry of HIV infection. However, this coreceptor promotes the entry of T-tropic HIV strains. Besides, CXCR4 coreceptors are mainly expressed in T cells. They are preferred by X-4 tropic viruses. Therefore, the main difference between CCR5 and CXCR4 receptors is their Promotion of HIV viral entry.

References:

1. Grande F, Occhiuzzi MA, Rizzuti B, Ioele G, De Luca M, Tucci P, Svicher V, Aquaro S, Garofalo A. CCR5/CXCR4 Dual Antagonism for the Improvement of HIV Infection Therapy. Molecules. 2019; 24(3):550.

Image Courtesy:

1. “HIV attachment.” By US National Institutes of Health – National Institute of Allergy and Infectious Diseases – Own work (Public Domain) via Commons Wikimedia
2. “3OE9 (CXCR4).” By S. Jähnichen – Own Work (CC-BY SA 3.0) via Commons Wikimedia