Research article

Early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells

Rina Das^1* , Rasha Hammamieh^1* , Roger Neill¹ , George V Ludwig² , Steven Eker³ , Patrick Lincoln³ , Preveen Ramamoorthy¹ , Apsara Dhokalia¹ , Sachin Mani¹ , Chanaka Mendis¹ , Christiano Cummings¹ , Brian Kearney⁴ , Atabak Royaee⁵ , Xiao-Zhe Huang⁶ , Chrysanthi Paranavitana⁶ , Leonard Smith² , Sheila Peel⁷ , Niranjan Kanesa-Thasan² , David Hoover⁶ , Luther E Lindler⁶ , David Yang⁵ , Erik Henchal² and Marti Jett^1,5

¹  Division of Pathology, Walter Reed Army Institute of Research, Silver Spring, MD, USA

²  Diagnostic Systems Division, United States Army Medical Research Institute of Infectious Diseases, USAMRIID, Ft. Detrick, Fredrick, MD, USA

³  Computer Science Laboratory, SRI International, Menlo Park, CA, USA

⁴  Geo-Centers, Inc. Rockville, MD; USA

⁵  Department of Chemistry, Georgetown University, Washington, DC, USA

⁶  Department of Bacterial & Rickettsial Diseases, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA

⁷  Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, MD, USA

author email corresponding author email* Contributed equally

BMC Infectious Diseases 2008, 8:104doi:10.1186/1471-2334-8-104

Published:	30 July 2008

Abstract

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.

Conclusion

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.