OBJECTIVE: The functional polarization of CD4 T cells determines their antimicrobial effector profile, but may also impact the susceptibility to infection with HIV-1. Here, we analyzed the susceptibility of CD4 T cells with different functional polarization to infection with X4 and R5-tropic HIV-1. METHODS: CD4 T cells with a Th1, Th2, Th17, and Th9 polarization were subjected to in-vitro infection assays with X4, R5, or vesicular stomatitis virus-G protein-pseudotyped HIV-1. In addition, we sorted differentially polarized CD4 T-cell subsets from individuals treated with antiretroviral therapy and analyzed the tropism of viral env sequences. RESULTS: Th9-polarized CD4 T cells and, to a lesser extent, Th2-polarized CD4 T cells expressed higher surface levels of CXCR4, and are more permissive to X4-tropic infection in vitro. In contrast, Th1 and Th17 CD4 T cells exhibited stronger surface expression of CCR5, and were more susceptible to infection with R5-tropic viruses. Correspondingly, the distribution of X4-tropic viral sequences in antiretroviral therapy-treated HIV-1-infected patients was biased toward Th9/Th2 cells, whereas R5-tropic sequences were more frequently observed in Th17 cells. CONCLUSION: CD4 T-cell polarization is associated with a distinct susceptibility to X4 and R5-tropic HIV-1 infection.
OBJECTIVE: The functional polarization of CD4 T cells determines their antimicrobial effector profile, but may also impact the susceptibility to infection with HIV-1. Here, we analyzed the susceptibility of CD4 T cells with different functional polarization to infection with X4 and R5-tropic HIV-1. METHODS:CD4 T cells with a Th1, Th2, Th17, and Th9 polarization were subjected to in-vitro infection assays with X4, R5, or vesicular stomatitis virus-G protein-pseudotyped HIV-1. In addition, we sorted differentially polarized CD4 T-cell subsets from individuals treated with antiretroviral therapy and analyzed the tropism of viral env sequences. RESULTS: Th9-polarized CD4 T cells and, to a lesser extent, Th2-polarized CD4 T cells expressed higher surface levels of CXCR4, and are more permissive to X4-tropic infection in vitro. In contrast, Th1 and Th17 CD4 T cells exhibited stronger surface expression of CCR5, and were more susceptible to infection with R5-tropic viruses. Correspondingly, the distribution of X4-tropic viral sequences in antiretroviral therapy-treated HIV-1-infectedpatients was biased toward Th9/Th2 cells, whereas R5-tropic sequences were more frequently observed in Th17 cells. CONCLUSION:CD4 T-cell polarization is associated with a distinct susceptibility to X4 and R5-tropic HIV-1 infection.
Authors: Mark Sharkey; Dunja Z Babic; Thomas Greenough; Roy Gulick; Daniel R Kuritzkes; Mario Stevenson Journal: PLoS Pathog Date: 2011-02-24 Impact factor: 6.823
Authors: Mohamed Abdel-Mohsen; Leticia Kuri-Cervantes; Judith Grau-Exposito; Adam M Spivak; Racheal A Nell; Costin Tomescu; Surya Kumari Vadrevu; Leila B Giron; Carla Serra-Peinado; Meritxell Genescà; Josep Castellví; Guoxin Wu; Perla M Del Rio Estrada; Mauricio González-Navarro; Kenneth Lynn; Colin T King; Sai Vemula; Kara Cox; Yanmin Wan; Qingsheng Li; Karam Mounzer; Jay Kostman; Ian Frank; Mirko Paiardini; Daria Hazuda; Gustavo Reyes-Terán; Douglas Richman; Bonnie Howell; Pablo Tebas; Javier Martinez-Picado; Vicente Planelles; Maria J Buzon; Michael R Betts; Luis J Montaner Journal: Sci Transl Med Date: 2018-04-18 Impact factor: 17.956
Authors: Thomas R O'Neil; Kevin Hu; Naomi R Truong; Sana Arshad; Barbara L Shacklett; Anthony L Cunningham; Najla Nasr Journal: Viruses Date: 2021-02-25 Impact factor: 5.048