Infectivity and host responses in Creutzfeldt-Jakob disease

Virology
L Manuelidis, W Fritch

Abstract

The relationship between viral titer and host responses was evaluated in Creutzfeldt-Jakob Disease (CJD). Rapid clearing of 97% of the virus from hamster brain occurred within 5 days, and residual virus was dispersed equally to both hemispheres. Exponential replication began only after a long eclipse phase of approximately 30 days, and by 100 days showed an > 3 log increase in titer. However, from 100 to 135 days, titers were restricted to plateau levels of approximately 10(8)/g. In comparison, previous studies show no appreciable eclipse phase and > or = 100-fold higher brain titers in hamster scrapie. Our calculations also revealed an effective doubling time (ti) of 7.6 days in CJD and a markedly different ti of approximately 3 days in scrapie. Thus different initiation and replication programs are encoded by each of these strains. The most pertinent host molecular responses included early astrocytic activity by 54 days, unaccompanied by morphological or behavioral changes. Changes in host PrP were minimal until 87 days when titers were already 2 x 10(7)/g. In the next 20 days 60% of brain PrP became resistant to limited proteolysis but total PrP did not increase. These fulminant PrP changes preceded viral arrest and subseque...Continue Reading

Citations

Jan 30, 2010·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Kohtaro Miyazawa, Laura Manuelidis
May 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Alvaro ArjonaLaura Manuelidis
Feb 3, 2007·Proceedings of the National Academy of Sciences of the United States of America·Laura ManuelidisBrian Mullins
Apr 15, 2003·Proceedings of the National Academy of Sciences of the United States of America·Laura Manuelidis, Zhi Yun Lu
Jul 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·M J ShlomchikL Manuelidis
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·L Manuelidis
Nov 8, 2008·Journal of Neurovirology·Ying LiuLaura Manuelidis
Jun 28, 2003·Viral Immunology·Laura Manuelidis
Aug 23, 2000·Journal of Virology·L ManuelidisW Fritch
Jan 15, 2003·Proceedings of the National Academy of Sciences of the United States of America·Christopher A Baker, Laura Manuelidis
Jan 22, 2005·Journal of Cellular Biochemistry·Zhi Yun LuLaura Manuelidis
Jul 28, 2011·Journal of Cellular Biochemistry·Kohtaro MiyazawaLaura Manuelidis
Jul 30, 2003·Biophysical Journal·R V KulkarniF Pázmándi
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Jan 17, 2016·Journal of Cellular Biochemistry·Sotirios Botsios, Laura Manuelidis
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Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·S B Prusiner
May 11, 1999·Journal of Virology·C A BakerL Manuelidis

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