Human immunodeficiency virus type 1 infection induces cyclin T1 expression in macrophages

被引:39
作者
Liou, LY [1 ]
Herrmann, CH [1 ]
Rice, AP [1 ]
机构
[1] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA
关键词
D O I
10.1128/JVI.78.15.8114-8119.2004
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The Tat protein of human immunodeficiency virus type 1 (HIV-1) is essential for viral replication and activates RNA polymerase R transcriptional elongation through the association with a cellular protein kinase composed of Cdk9 and cyclin T1. Tat binds to this kinase complex through a direct protein-protein interaction with cyclin T1. Monocytes/macrophages are important targets of HIV-1 infection, and previous work has shown that cyclin T1 but not Cdk9 protein expression is low in monocytes isolated from blood. While Cdk9 expression is expressed at a high level during monocyte differentiation to macrophages in vitro, cyclin T1 expression is induced during the first few days of differentiation and is shut off after 1 to 2 weeks. We show here that the shutoff of cyclin T1 expression in late-differentiated macrophages involves proteasome-mediated proteollysis. We also show that cyclin T1 can be reinduced by a number of pathogen-associated molecular patterns that activate macrophages, indicating that up-regulation of cyclin T1 is part of an innate immune response. Furthermore, we found that HIV-1 infection early in macrophage differentiation results in sustained cyclin T1 expression, while infection at late times in differentiation results in the reinduction of cyclin T1. Expression of the viral Nef protein from an adenovirus vector suggests that Nef contributes to the HIV-1 induction of cyclin T1. These findings suggest that HIV-1 infection hijacks a component of the innate immune response in macrophages that results in enhancement rather than inhibition of viral replication.
引用
收藏
页码:8114 / 8119
页数:6
相关论文
共 29 条
  • [1] Antiapoptotic function of Cdk9 (TAK/P-TEFb) in U937 promonocytic cells
    Foskett, SM
    Ghose, R
    Tang, DN
    Lewis, DE
    Rice, AP
    [J]. JOURNAL OF VIROLOGY, 2001, 75 (03) : 1220 - 1228
  • [2] HIV-1 Tat: coping with negative elongation factors
    Garber, ME
    Jones, KA
    [J]. CURRENT OPINION IN IMMUNOLOGY, 1999, 11 (04) : 460 - 465
  • [3] CDK9 is constitutively expressed throughout the cell cycle, and its steady-state expression is independent of SKP2
    Garriga, J
    Bhattacharya, S
    Calbó, J
    Marshall, RM
    Truongcao, M
    Haines, DS
    Graña, X
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (15) : 5165 - 5173
  • [4] Increased association of 7SK snRNA with Tat cofactor P-TEFb following activation of peripheral blood lymphocytes
    Haaland, RE
    Herrmann, CH
    Rice, AP
    [J]. AIDS, 2003, 17 (17) : 2429 - 2436
  • [5] Viral transactivators specifically target distinct cellular protein kinases that phosphorylate the RNA polymerase II C-terminal domain
    Herrmann, CH
    Gold, MO
    Rice, AP
    [J]. NUCLEIC ACIDS RESEARCH, 1996, 24 (03) : 501 - 508
  • [7] INFECTION OF MONOCYTE MACROPHAGES BY HUMAN T-LYMPHOTROPIC VIRUS TYPE-III
    HO, DD
    ROTA, TR
    HIRSCH, MS
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1986, 77 (05) : 1712 - 1715
  • [8] Domains in the SPT5 protein that modulate its transcriptional regulatory properties
    Ivanov, D
    Kwak, YT
    Guo, J
    Gaynor, RB
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (09) : 2970 - 2983
  • [9] Tackling Tat
    Karn, J
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1999, 293 (02) : 235 - 254
  • [10] Interaction between cyclin T1 and SCFSKP2 targets CDK9 for ubiquitination and degradation by the proteasome
    Kiernan, RE
    Emiliani, S
    Nakayama, E
    Castro, A
    Labbé, JC
    Lorca, T
    Nakayama, K
    Benkirane, A
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (23) : 7956 - 7970