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.
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http://dx.doi.org/10.1038/srep44894 | DOI Listing |
mBio
August 2023
Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom.
The HIV-1 Vpu protein is expressed late in the virus lifecycle to promote infectious virus production and avoid innate and adaptive immunity. This includes the inhibition of the NF-κB pathway which, when activated, leads to the induction of inflammatory responses and the promotion of antiviral immunity. Here we demonstrate that Vpu can inhibit both canonical and non-canonical NF-κB pathways, through the direct inhibition of the F-box protein β-TrCP, the substrate recognition portion of the Skp1-Cul1-F-box (SCF) ubiquitin ligase complex.
View Article and Find Full Text PDFAIDS Res Hum Retroviruses
December 2021
Division of Infection and Immunity, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.
HIV-1 escapes by acquiring mutations that differentially influence the course of infection. Unlike HIV-1 structural and enzymatic proteins, it remains elusive what extent the host immune-mediated selection pressure influences the variability of the accessory (Vif, Vpu, Vpr, and Nef) and regulatory (Tat and Rev) proteins. To address this, we analyzed the viral sequences encoding accessory and regulatory proteins from 446 human leukocyte antigen (HLA)-typed, chronically HIV-1 subtype B-infected, and treatment-naive individuals in Japan.
View Article and Find Full Text PDFAIDS
July 2021
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia.
Objective S: We investigated the relationship between human leukocyte antigen (HLA)-associated preadaptation for the entire subtype C HIV-1 proteome of the transmitted founder virus and subsequent HIV-1 disease progression in a cohort of heterosexual linked transmission pairs in Zambia.
Design: An adaptation model was used to calculate an adaptation score for each virus-HLA combination in order to quantify the degree of preadaptation of the transmitted virus to the linked recipient's HLA alleles. These scores were then assessed for their relationship to viral load and longitudinal CD4+ decline in the recipient.
Proteins
December 2018
Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
Epitope mapping has emerged as a powerful tool to develop peptide vaccines against hypervariable viruses such as HIV. This method has led to stimulate a specific immune response and achieve advanced vaccine formulations. In this study, we identified peptides that were potentially immunostimulatory and highly conserved in HIV-1 main group.
View Article and Find Full Text PDFPLoS Pathog
September 2018
Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington DC, United States of America.
HIV-1 can downregulate HLA-C on infected cells, using the viral protein Vpu, and the magnitude of this downregulation varies widely between primary HIV-1 variants. The selection pressures that result in viral downregulation of HLA-C in some individuals, but preservation of surface HLA-C in others are not clear. To better understand viral immune evasion targeting HLA-C, we have characterized HLA-C downregulation by a range of primary HIV-1 viruses.
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