The observations that the anti-CXCR4 N-terminus mAb (clone A145) showed little or no inhibition, and the anti-CXCR4 ECL3 mAb (clone A80) was not as potent in inhibiting HIV-1 infection, as compared with the A120 mAb, indicate that the ligation via the ECL1 and/or ECL2 domains is critical for the inhibition of R5 and X4 HIV-1 infection. Here, CXCR4 is linked to HIV-1 infection.