The key difference between CCR5 and CXCR4 is their role in HIV infection. During the early stages of HIV infection, viral isolates tend to use CCR5 for viral entry; hence M-tropic virus strains predominate during the early phase of infection. In contrast, the later isolates tend to use CXCR4 for viral entry; hence T-tropic virus strains occur late during disease progression to AIDS.
HIV virus uses CD4 cell as the primary receptor for entry into human cells. In addition, CCR5 and CXCR4 are two types of predominant chemokine receptors used as coreceptors in HIV-1 entry. Therefore, the expression of these coreceptors is critical for determining viral tropism.
A wide variety of HIV-1 strains use these two coreceptors. CXCR4 and CCR5 represent the model coreceptors for the entry of T-tropic and M-tropic HIV-1 strains, respectively. Generally, viral isolates use CCR5 coreceptors during the early stages of HIV infection while later isolates use CXCR4 coreceptors. Blocking the CCR5 and CXCR4 coreceptors is a way of preventing HIV from infecting new cells. Therefore, researchers are developing methods for directly blocking these receptor sites.
CONTENTS
1. Overview and Key Difference
2. What is CCR5
3. What is CXCR4
4. Similarities Between CCR5 and CXCR4
5. Side by Side Comparison – CCR5 vs CXCR4 in Tabular Form
6. Summary
What is CCR5?
CCR5 is a chemokine coreceptor which is a seven-transmembrane G-protein coupled receptor. It is a hydrophobic protein which cannot be purified easily. CCR5 coreceptor is present on a broad range of cells, including T-cells and macrophages. There are seven potential phosphorylation sites in CCR5. CCR5 allows entry of M-tropic HIV-1 strains. M-trophic or macrophage-tropic HIV strains are most common in early disease, and these viruses tend to use CCR5 coreceptors for viral entry. M-trophic HIV strains are the most common sexually transmitted form of the virus. Therefore, CCR5 appears to be important for M-trophic strains.
Figure 01: CCR5 Coreceptor
What is CXCR4?
Similar to CCR5, CXCR4 is a chemokine coreceptor that facilitates HIV-1 entry into human cells. It is also a seven-transmembrane G-coupled receptor. CXCR4 coreceptors are primarily found on CD4+ cells. There are 21 potential phosphorylation sites in CXCR4.
Figure 02: CXCR4 Coreceptor
T-trophic HIV strains which are found during the late in infection use CXCR4 coreceptors. CXCR4 is encoded by the CXCR4 gene.
What are the Similarities Between CCR5 and CXCR4?
- CCR5 and CXCR4 are HIV coreceptors.
- Both are predominant chemokine receptors located on the surface of white blood cells.
- They are activated by the binding of one or more chemokines.
- Structurally, they are seven-transmembrane G-protein coupled receptors.
- They function as coreceptors for HIV-1 entry into CD4+ cells.
- There are CCR5 blocking agents and CXCR4-based blocking agents.
- Both CCR5 and CXCR4 proteins are highly hydrophobic and cannot be readily purified.
What is the Difference Between CCR5 and CXCR4?
CCR5 is a chemokine coreceptor that allows entry of M-trophic HIV strains into human cells while CXCR4 is a chemokine coreceptor that promotes entry of T-tropic HIV-1 strains into human cells. M-trophic HIV strains use CCR5 coreceptors for a viral entry during the early stage of viral infection while T-trophic HIV strains use CXCR4 coreceptors for a viral entry during the late in infection. So, this is the key difference between CCR5 and CXCR4.
Below infographic shows more details of the difference between CCR5 and CXCR4.
Summary – CCR5 vs CXCR4
CCR5 and CXCR4 are two proteins expressed on the surface of host immune cells. They belong to the family of seven transmembrane G-protein-coupled chemokine receptors. These two receptors act as coreceptors for HIV entry into human cells. M-trophic HIV strains use CCR5 coreceptors for a viral entry during the early stage of viral infection while T-trophic HIV strains use CXCR4 coreceptors for a viral entry during the late in infection. Both coreceptors are activated by the binding of one or more chemokines. Thus, this summarizes the difference between CCR5 and CXCR4.
Reference:
1. Bleul, C C, et al. “The HIV Coreceptors CXCR4 and CCR5 Are Differentially Expressed and Regulated on Human T Lymphocytes.” Proceedings of the National Academy of Sciences of the United States of America, The National Academy of Sciences of the USA, 4 Mar. 1997, Available here.
2. Alkhatib, Ghalib. “The Biology of CCR5 and CXCR4.” Current Opinion in HIV and AIDS, U.S. National Library of Medicine, Mar. 2009, Available here.
Image Courtesy:
1. “HIV attachment” By US National Institutes of Health – National Institute of Allergy and Infectious Diseases – US National Institutes of Health – National Institute of Allergy and Infectious Diseases (Public Domain) via Commons Wikimedia
2. “3OE9 (CXCR4)” By S. Jähnichen – Own work (CC BY-SA 3.0) via Commons Wikimedia