title: A dichotomy in cortical actin and chemotactic actin activity between human memory and naive T cells contributes to their differential susceptibility to HIV-1 infection.
abstract: Human memory and naive CD4 T cells can mainly be identified by the reciprocal expression of the CD45RO or CD45RA isoforms. In HIV-1 infection, blood CD45RO memory CD4 T cells are preferentially infected and serve as a major viral reservoir. The molecular mechanism dictating this differential susceptibility to HIV-1 remains largely obscure. Here, we report that the different susceptibility of memory and naive T cells to HIV is not determined by restriction factors such as Apobec3G or BST2. However, we observed a phenotypic distinction between human CD45RO and CD45RA resting CD4 T cells in their cortical actin density and actin dynamics. CD45RO CD4 T cells possess a higher cortical actin density and can be distinguished as CD45RO(+)Actin(high). In contrast, CD45RA T cells are phenotypically CD45RA(+)Actin(low). In addition, the cortical actin in CD45RO memory CD4 T cells is more dynamic and can respond to low dosages of chemotactic induction by SDF-1, whereas that of naive cells cannot, despite a similar level of the chemokine receptor CXCR4 present on both cells. We further demonstrate that this difference in the cortical actin contributes to their differential susceptibility to HIV-1; resting memory but not naive T cells are highly responsive to HIV-mediated actin dynamics that promote higher levels of viral entry and early DNA synthesis in resting memory CD4 T cells. Furthermore, transient induction of actin dynamics in resting naive T cells rescues HIV latent infection following CD3/CD28 stimulation. These results suggest a key role of chemotactic actin activity in facilitating HIV-1 latent infection of these T cell subsets.
authors.affiliation: National Center for Biodefense and Infectious Diseases, Department of Molecular and Microbiology, George Mason University, Manassas, Virginia 20110.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Wang
authors.affiliation: National Center for Biodefense and Infectious Diseases, Department of Molecular and Microbiology, George Mason University, Manassas, Virginia 20110.
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.affiliation: National Center for Biodefense and Infectious Diseases, Department of Molecular and Microbiology, George Mason University, Manassas, Virginia 20110.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Yu
authors.affiliation: National Center for Biodefense and Infectious Diseases, Department of Molecular and Microbiology, George Mason University, Manassas, Virginia 20110.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Vorster
authors.affiliation: Mucosal Immunology Section, Oral Infection and Immunity Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: WanJun
authors.initials: W
authors.lastname: Chen
authors.affiliation: National Center for Biodefense and Infectious Diseases, Department of Molecular and Microbiology, George Mason University, Manassas, Virginia 20110. Electronic address: ywu8@gmu.edu.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000071480:APOBEC-3G Deaminase; D000199:Actins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D000199:Actins; D018106:CD28 Antigens; D017252:CD3 Complex; C527276:CXCR4 protein, human; D004279:DNA, Viral; D019718:Receptors, CXCR4; D017493:Leukocyte Common Antigens; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase