Minor contribution of HLA class I-associated selective pressure to the variability of HIV-1 accessory protein Vpu

► We examined HLA-I-associated polymorphisms in the HIV accessory protein Vpu. ► We identified only 4 HLA-associated mutations in all reading frames in Vpu. ► We identified rather 103 codon-codon covariation associations within Vpu. ► Vpu is less influenced by HLA-I-associated immunity than other HIV-1 accessory proteins.