Research

Synergistic effect of human CycT1 and CRM1 on HIV-1 propagation in rat T cells and macrophages

Hiroyuki Okada¹ , Xianfeng Zhang¹ , Ismael Ben Fofana^1,2 , Mika Nagai¹ , Hajime Suzuki¹ , Takashi Ohashi¹ and Hisatoshi Shida¹

¹  Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815, Japan

²  Microbiology Division, New England Primate Research Center, Harvard Medical School, One Pine Hill Drive, Southborough, Maryland 01772, USA

author email corresponding author email

Retrovirology 2009, 6:43doi:10.1186/1742-4690-6-43

Published:	12 May 2009

Abstract

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.

Conclusion

The expression of both hCycT1 and hCRM1 appears to be fundamental to developing a rat model that supports robust propagation of HIV-1.