HIV-1 uses multiple co-receptors for entry into cells. What is the significance of the CCR5Δ32 homozygous mutation in individuals exposed to HIV-1 R5 strains?

• A Increased susceptibility to HIV-1 X4 strains
• B Accelerated progression to AIDS
• C Resistance to all HIV-1 strains including X4 strains
• D Complete resistance to R5 HIV-1 infection due to absence of CCR5 co-receptor on macrophages and T cells ✓

Explanation

CCR5 is the co-receptor for macrophage-tropic (R5) HIV-1 strains that predominate in early infection. Individuals homozygous for the CCR5Δ32 deletion (a 32-bp deletion causing frameshift and non-functional truncated protein) lack surface CCR5 expression; they are virtually resistant to R5 HIV-1 infection. This mutation is present in ~1% of Northern Europeans. X4 strains use CXCR4 as co-receptor and are NOT affected by CCR5Δ32 mutation. Heterozygotes have partial protection and slower disease progression.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

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