HIV-1 enters CD4+ T cells through its gp120-gp41 envelope complex. After gp120 binds CD4 and a co-receptor, gp41 mediates fusion. Which co-receptor is preferentially used by macrophage-tropic (R5) strains of HIV-1, and why is this important for transmission?
- A CCR5; present on mucosal CD4+ T cells and macrophages; mutations in CCR5 (Δ32) confer resistance to transmission ✓
- B CXCR4; used by syncytium-inducing strains that preferentially infect naive T cells
- C CCR3; expressed on eosinophils facilitating gut mucosal entry
- D CXCR3; facilitates central nervous system invasion
Explanation
R5-tropic HIV-1 strains (also called M-tropic) use CCR5 as a co-receptor. These strains are predominantly transmitted sexually and dominate early infection because mucosal dendritic cells and CD4+ T cells in the genital tract/rectal mucosa express high CCR5. Individuals homozygous for the 32-bp deletion in CCR5 (CCR5-Δ32) lack surface CCR5 and are highly resistant to HIV-1 infection. This discovery led to maraviroc (CCR5 antagonist) as an antiretroviral. X4-tropic strains use CXCR4, emerge late in disease, and correlate with rapid CD4 decline. The Berlin patient was cured after an allogeneic stem cell transplant from a CCR5-Δ32 donor.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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