Increased expression with differential subcellular location of cytidine deaminase APOBEC3G in human CD4+ T-cell activation and dendritic cell maturation

被引：13

作者：

Oliva, Harold ^{[1
,13
]}

Pacheco, Rodrigo ^{[2
,3
]}

Martinez-Navio, Jose M. ^{[4
,14
]}

Rodriguez-Garcia, Marta ^{[1
,5
,15
]}

Naranjo-Gomez, Mar ^{[6
,16
,17
]}

Climent, Nuria ^{[1
]}

Prado, Carolina ^{[3
]}

Gil, Cristina ^{[1
]}

Plana, Montserrat ^{[1
]}

Garcia, Felipe ^{[1
,7
,8
]}

Miro, Jose M. ^{[1
,7
,8
]}

Franco, Rafael ^{[4
,9
]}

Borras, Francesc E. ^{[10
,11
]}

Navaratnam, Naveenan ^{[12
]}

Gatell, Jose M. ^{[1
,7
,8
]}

Gallart, Teresa ^{[1
,5
]}

机构：

[1] Univ Barcelona, Fac Med, Hosp Clin Barcelona, Inst Invest Biomed August Pi i Sunyer IDIBAPS,AID, Barcelona, Spain

[2] Univ Andres Bello, Fac Ciencias Biol, Dept Ciencias Biol, Santiago, Chile

[3] Fdn Ciencia & Vida, Lab Neuroinmunol, Santiago, Chile

[4] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, Barcelona, Spain

[5] Hosp Clin Univ Barcelona, Serv Immunol, Villarroel 170, Barcelona 08036, Spain

[6] Autonomous Univ Barcelona, Inst Invest Germans Trias Pujol, LIRAD Lab Immunobiol Res & Diagnost Applicat, Badalona, Barcelona, Spain

[7] Hosp Clin Barcelona, Infect Dis Serv, Barcelona, Spain

[8] Hosp Clin Barcelona, AIDS Unit, Barcelona, Spain

[9] Inst Salud Carlos III, CIBERNED Ctr Invest Red Enfermedades Neurodegener, Madrid, Spain

[10] Inst Invest Germans Trias & Pujol IGTP, IVECAT Grp, Badalona, Spain

[11] Germans Trias & Pujol Univ Hosp, Serv Nephrol, Badalona, Spain

[12] Imperial Coll London, MRC, Ctr Clin Sci, Hammersmith Hosp Campus, London, England

[13] Veterquim SA, Res & Dev Lab, Santiago, Chile

[14] Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33136 USA

[15] Dartmouth Med Sch, Dept Physiol & Neurobiol, Lebanon, NH USA

[16] Inst Genet Mol Montpellier, UMR 5535, CNRS, Montpellier, France

[17] Univ Montpellier, Montpellier, France

来源：

IMMUNOLOGY AND CELL BIOLOGY | 2016年 / 94卷 / 07期

基金：

英国医学研究理事会;

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; MESSENGER-RNA LEVELS; ALU RETROTRANSPOSITION; L1; RETROTRANSPOSITION; INTRINSIC RESISTANCE; PRIMARY LYMPHOCYTES; HIV-1; REPLICATION; FAMILY PROTEINS; EDITING ENZYME; INFECTION;

D O I：

10.1038/icb.2016.28

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

APOBEC3G (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G; A3G) is an innate defense protein showing activity against retroviruses and retrotransposons. Activated CD4(+) T cells are highly permissive for HIV-1 replication, whereas resting CD4(+) T cells are refractory. Dendritic cells (DCs), especially mature DCs, are also refractory. We investigated whether these differences could be related to a differential A3G expression and/or subcellular distribution. We found that A3G mRNA and protein expression is very low in resting CD4(+) T cells and immature DCs, but increases strongly following T-cell activation and DC maturation. The Apo-7 anti-A3G monoclonal antibody (mAb), which was specifically developed, confirmed these differences at the protein level and disclosed that A3G is mainly cytoplasmic in resting CD4(+) T cells and immature DCs. Nevertheless, A3G translocates to the nucleus in activated-proliferating CD4(+) T cells, yet remaining cytoplasmic in matured DCs, a finding confirmed by immunoblotting analysis of cytoplasmic and nuclear fractions. Apo-7 mAb was able to immunoprecipitate endogenous A3G allowing to detect complexes with numerous proteins in activated-proliferating but not in resting CD4(+) T cells. The results show for the first time the nuclear translocation of A3G in activated-proliferating CD4(+) T cells.

引用

页码：689 / 700

页数：12

共 74 条

[1] Interactions of host APOBEC3 restriction factors with HIV-1 in vivo: implications for therapeutics [J].