Early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells.
BACKGROUND
Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs.


METHODS
To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays.


RESULTS
We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized B. anthracis spores and 30 min post exposure to a bacterial toxin.


CONCLUSIONS
Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents.
Das
Rina
R
Division of Pathology, Walter Reed Army Institute of Research, Silver Spring, MD, USA. dasr2@nhlbi.nih.gov
Hammamieh
Rasha
R
Neill
Roger
R
Ludwig
George V
GV
Eker
Steven
S
Lincoln
Patrick
P
Ramamoorthy
Preveen
P
Dhokalia
Apsara
A
Mani
Sachin
S
Mendis
Chanaka
C
Cummings
Christiano
C
Kearney
Brian
B
Royaee
Atabak
A
Huang
Xiao-Zhe
XZ
Paranavitana
Chrysanthi
C
Smith
Leonard
L
Peel
Sheila
S
Kanesa-Thasan
Niranjan
N
Hoover
David
D
Lindler
Luther E
LE
Yang
David
D
Henchal
Erik
E
Jett
Marti
M
D000704:Analysis of Variance; D000818:Animals; D000881:Anthrax / Q000235:genetics; D001408:Bacillus anthracis / Q000276:immunology*; D054045:Biological Warfare Agents; D004781:Environmental Exposure; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008253:Macaca mulatta; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013997:Time Factors
D054045:Biological Warfare Agents; D012313:RNA