The host response to smallpox: Analysis of the gene expression program in peripheral blood cells in a nonhuman primate model

作者: K. H. Rubins , L. E. Hensley , P. B. Jahrling , A. R. Whitney , T. W. Geisbert

DOI: 10.1073/PNAS.0405759101

关键词:

摘要: Smallpox has played an unparalleled role in human history and remains a significant potential threat to public health. Despite the historical significance of this disease, we know little about underlying pathophysiology or virulence mechanisms causative agent, variola virus. To improve our understanding pathogenesis variola-host interactions, examined molecular cellular features hemorrhagic smallpox cynomolgus macaques. We used cDNA microarrays analyze host gene expression patterns sequential blood samples from each 22 infected animals. Variola infection elicited striking temporally coordinated peripheral blood. Of particular interest were that appear represent IFN response, cell proliferation, immunoglobulin expression, viral dose-dependent patterns, modulation immune response. The virtual absence tumor necrosis factor α/NF-κB-activated transcriptional program face overwhelming systemic suggests products may ablate These results provide detailed picture response during infection, help guide development diagnostic, therapeutic, prophylactic strategies.

参考文章(36)
Ena Wang, Lance D. Miller, Galen A. Ohnmacht, Edison T. Liu, Francesco M. Marincola, High-fidelity mRNA amplification for gene profiling. Nature Biotechnology. ,vol. 18, pp. 457- 459 ,(2000) , 10.1038/74546
Frank Fenner, Smallpox and its eradication World Health Organization. ,(1988)
P. B. Jahrling, L. E. Hensley, M. J. Martinez, J. W. LeDuc, K. H. Rubins, D. A. Relman, J. W. Huggins, Exploring the potential of variola virus infection of cynomolgus macaques as a model for human smallpox Proceedings of the National Academy of Sciences of the United States of America. ,vol. 101, pp. 15196- 15200 ,(2004) , 10.1073/PNAS.0405954101
S. Polyak, H. Chen, D. Hirsch, I. George, R. Hershberg, K. Sperber, Impaired class II expression and antigen uptake in monocytic cells after HIV-1 infection. Journal of Immunology. ,vol. 159, pp. 2177- 2188 ,(2005) , 10.4049/JIMMUNOL.175.12.8444
Antonio Alcami, Ulrich H. Koszinowski, Viral mechanisms of immune evasion Immunology Today. ,vol. 21, pp. 447- 455 ,(2000) , 10.1016/S0167-5699(00)01699-6
Jing Gao, Bishnu P. De, Yulong Han, Suresh Choudhary, Richard Ransohoff, Amiya K. Banerjee, Human parainfluenza virus type 3 inhibits gamma interferon-induced major histocompatibility complex class II expression directly and by inducing alpha/beta interferon. Journal of Virology. ,vol. 75, pp. 1124- 1131 ,(2001) , 10.1128/JVI.75.3.1124-1131.2001
Robert F. Massung, Li-Ing Liu, Jin Qi, Janice C. Knight, Thomas E. Yuran, Anthony R. Kerlavage, Joseph M. Parsons, J.Craig Venter, Joseph J. Esposito, Analysis of the complete genome of smallpox variola major virus strain Bangladesh-1975. Virology. ,vol. 201, pp. 215- 240 ,(1994) , 10.1006/VIRO.1994.1288
A. I. Su, M. P. Cooke, K. A. Ching, Y. Hakak, J. R. Walker, T. Wiltshire, A. P. Orth, R. G. Vega, L. M. Sapinoso, A. Moqrich, A. Patapoutian, G. M. Hampton, P. G. Schultz, J. B. Hogenesch, Large-scale analysis of the human and mouse transcriptomes Proceedings of the National Academy of Sciences of the United States of America. ,vol. 99, pp. 4465- 4470 ,(2002) , 10.1073/PNAS.012025199
P STROOBANT, A RICE, W GULLICK, D CHENG, I KERR, M WATERFIELD, Purification and characterization of vaccinia virus growth factor. Cell. ,vol. 42, pp. 383- 393 ,(1985) , 10.1016/S0092-8674(85)80133-1
Daniel M. Miller, Brian M. Rahill, Jeremy M. Boss, Michael D. Lairmore, Joan E. Durbin, James W. Waldman, Daniel D. Sedmak, Human Cytomegalovirus Inhibits Major Histocompatibility Complex Class II Expression By Disruption of the Jak/Stat Pathway Journal of Experimental Medicine. ,vol. 187, pp. 675- 683 ,(1998) , 10.1084/JEM.187.5.675