Synergistic effect of human CycT1 and CRM1 on HIV-1 propagation in rat T cells and macrophages.
BACKGROUND
In vivo studies of HIV-1 pathogenesis and testing of antiviral strategies have been hampered by the lack of an immunocompetent small animal model that is highly susceptible to HIV-1 infection. Although transgenic rats that express the HIV-1 receptor complex hCD4 and hCCR5 are susceptible to infection, HIV-1 replicates very poorly in these animals. To demonstrate the molecular basis for developing a better rat model for HIV-1 infection, we evaluated the effect of human CyclinT1 (hCycT1) and CRM1 (hCRM1) on Gag p24 production in rat T cells and macrophages using both established cell lines and primary cells prepared from hCycT1/hCRM1 transgenic rats.


RESULTS
Expression of hCycT1 augmented Gag production 20-50 fold in rat T cells, but had little effect in macrophages. Expression of hCRM1 enhanced Gag production 10-15 fold in macrophages, but only marginally in T cells. Expression of both factors synergistically enhanced p24 production to levels approximately 10-40% of those detected in human cells. R5 viruses produced in rat T cells and macrophages were fully infectious.


CONCLUSIONS
The expression of both hCycT1 and hCRM1 appears to be fundamental to developing a rat model that supports robust propagation of HIV-1.
Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815, Japan. hiro1230@igm.hokudai.ac.jp
Hiroyuki
H
Okada
Xianfeng
X
Zhang
Ismael
I
Ben Fofana
Mika
M
Nagai
Hajime
H
Suzuki
Takashi
T
Ohashi
Hisatoshi
H
Shida
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D056906:Cyclin T; D016213:Cyclins / Q000096:biosynthesis*; D004195:Disease Models, Animal; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D028884:Karyopherins / Q000096:biosynthesis*; D008264:Macrophages / Q000821:virology*; D051381:Rats; D055647:Rats, Transgenic; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000821:virology*; D014779:Virus Replication; D000097606:Exportin 1 Protein
D056906:Cyclin T; D016213:Cyclins; D016655:HIV Core Protein p24; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein; C503684:CCNT1 protein, human