GENETIC CHARACTERIZATION OF HIV-1 VPU GENE FROM VIROLOGICALLY SUPPRESSED HIV-1-INFECTED OLDER PATIENTS ON LONG-TERM ANTIRETROVIRAL THERAPY

Abstract

Although advancements in antiretroviral therapy (ART) have been able to control HIV infection such that patients achieve suppressed viral loads and recovered CD4 T cell counts, the virus continues to persist in latent reservoirs. In order to develop potential strategies for HIV-1 eradications, its important to characterize the molecular, biological and immunological features of HIV-1 genes from virologically suppressed patients. One such gene is the HIV-1 accessory gene, vpu that plays an important role in virion release from infected cells. In addition, Vpu is involved in BST-2 degradation, CD4 downregulation and pathogenesis, and may influence persistence of HIV-1 in viral reservoirs. In this study, the vpu genes from 21 HIV-infected older patients with suppressed viremia (mostly undetectable viral load) due to long-term ART were analyzed. Phylogenetic analysis demonstrated that each of the 21 patients’ vpu sequences were well discriminated and separated from each other and clustered within their subtrees. The vpu sequences from our 21 patients exhibited a low degree genetic variability, lower estimates of genetic diversity and most patient sequences were not under positive selection pressure. In addition, 82% of the Vpu deduced amino acid sequences had intact and open reading frames and most sequences had conservation of the functional domains required for Vpu activity, including virus release, BST-2 degradation, oligomerization and CD4 degradation. Furthermore, the deduced amino acid sequences showed a higher level of variability in the previously identified CTL epitope in Vpu, suggesting escape mutants. In summary, a low degree of genetic diversity and conservation of functional motifs/domain for Vpu activity and high variability in the CTL epitope were key features of the vpu gene in these 21 HIV-infected older patients on ART with suppressed viremia.