1. Differential Vpu-Mediated CD4 and Tetherin Downregulation Functions among Major HIV-1 Group M Subtypes
- Author
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Umviligihozo, Gisele, Cobarrubias, Kyle D, Chandrarathna, Sandali, Jin, Steven W, Reddy, Nicole, Byakwaga, Helen, Muzoora, Conrad, Bwana, Mwebesa B, Lee, Guinevere Q, Hunt, Peter W, Martin, Jeff N, Brumme, Chanson J, Bangsberg, David R, Karita, Etienne, Allen, Susan, Hunter, Eric, Ndung’u, Thumbi, Brumme, Zabrina L, and Brockman, Mark A
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,HIV/AIDS ,Sexually Transmitted Infections ,Infectious Diseases ,Genetics ,2.2 Factors relating to the physical environment ,2.1 Biological and endogenous factors ,Infection ,Antigens ,CD ,CD4 Antigens ,Cell Line ,Transformed ,Chronic Disease ,Down-Regulation ,GPI-Linked Proteins ,HIV Infections ,HIV-1 ,Human Immunodeficiency Virus Proteins ,Humans ,Viral Regulatory and Accessory Proteins ,CD4 ,subtype ,tetherin ,Vpu ,Downregulation ,Biological Sciences ,Agricultural and Veterinary Sciences ,Medical and Health Sciences ,Virology ,Agricultural ,veterinary and food sciences ,Biological sciences ,Biomedical and clinical sciences - Abstract
Downregulation of BST-2/tetherin and CD4 by HIV-1 viral protein U (Vpu) promotes viral egress and allows infected cells to evade host immunity. Little is known however about the natural variability in these Vpu functions among the genetically diverse viral subtypes that contribute to the HIV-1 pandemic. We collected Vpu isolates from 332 treatment-naive individuals living with chronic HIV-1 infection in Uganda, Rwanda, South Africa, and Canada. Together, these Vpu isolates represent four major HIV-1 group M subtypes (A [n = 63], B [n = 84], C [n = 94], and D [n = 59]) plus intersubtype recombinants and uncommon strains (n = 32). The ability of each Vpu clone to downregulate endogenous CD4 and tetherin was quantified using flow cytometry following transfection into an immortalized T-cell line and compared to that of a reference Vpu clone derived from HIV-1 subtype B NL4.3. Overall, the median CD4 downregulation function of natural Vpu isolates was similar to that of NL4.3 (1.01 [interquartile range {IQR}, 0.86 to 1.18]), while the median tetherin downregulation function was moderately lower than that of NL4.3 (0.90 [0.79 to 0.97]). Both Vpu functions varied significantly among HIV-1 subtypes (Kruskal-Wallis P
- Published
- 2020