Functional Conservation and Coherence of HIV-1 Subtype A Vpu Alleles
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Functional studies of HIV-1 proteins are normally conducted using lab adapted strains of HIV-1. The extent of those functions in clinical strains is sometimes unknown. In this study, we amplified and sequenced HIV-1 Vpu from 10 Iranian patients infected with HIV-1. Phylogenetic analysis indicated that the Vpu alleles were closely related to the CRF35_AD from Iran and subtype A Vpu. We addressed some of the well-established functions of the HIV-1 Vpu, as well as some of its recently reported functions. Ability of the clinical strains of subtype A Vpu alleles for downregulation of CD4 was similar to that of the lab adapted NL4.3 Vpu. Majority of the subtype A Vpu alleles performed stronger than NL4.3 Vpu for downregulation of SNAT1. The Vpu alleles differentially induced downregulation of HLA-C, ranging from no effect to 88% downregulation of surface HLA-C. Downregulation of tetherin and enhancement of virus release was similar for the subtype A Vpu alleles and NL4.3. Subtype A Vpu alleles were more potent when compared with NL4.3 for inhibition of NF-κB activation. Our study shows that subtype A Vpu alleles exert the classical functions of HIV-1 Vpu.
Umviligihozo G, Cobarrubias K, Chandrarathna S, Jin S, Reddy N, Byakwaga H J Virol. 2020; 94(14).
PMID: 32376625 PMC: 7343213. DOI: 10.1128/JVI.00293-20.
HLA-C downregulation by HIV-1 adapts to host HLA genotype.
Bachtel N, Umviligihozo G, Pickering S, Mota T, Liang H, Del Prete G PLoS Pathog. 2018; 14(9):e1007257.
PMID: 30180214 PMC: 6138419. DOI: 10.1371/journal.ppat.1007257.