Blood Safety: Infectious Agent Interventions and Development of Storage Biomarkers for Blood Cells and Related Products

Principal Investigator: C. D. Atreya, PhD
Office / Division / Lab: OBRR / DH / LCH

---

Overview

Public Health Issue: I. A combination of effective single-step nonspecific pathogen reduction , followed by high sensitivity detection of residual pathogens is ideal for the safety of blood, blood components and related products used in transfusion medicine. However, existing technologies have proven to be associated with adverse reactions in treated subjects. II. Key cellular components of blood in transfusion medicine are red blood cell concentrates (RBCs) and platelet concentrates (PCs). During storage, these cellular components undergo physiological changes often collectively referred to as 'storage lesions', which adversely affect their survival in vivo following transfusion.

Regulatory Contribution: I. Development of novel proof-of-concepts for pathogen reduction, which are different from the current ones that outweigh the associated toxicity and/or contamination risk, followed by high sensitivity detection methods for residual pathogens in the blood and its components will enhance the safety margin. II. Identifying biomarkers that truly reflect the cellular status at any given time during storage would help in developing nonclinical efficacy biomarkers for stored platelets.

Research Approach: I. A panel of selected novel antimicrobials are being evaluated for their capacity to simultaneously destroy bacteria and parasites in blood, blood components and plasma. Similarly, custom made synthetic peptides conjugated to nanoparticle-based quantum dots are utilized to detect a panel of bacteria that are important to the transfusion medicine as well as to bio-defense. II. Genomic and proteomic approaches are used to identify appropriate cellular markers suitable to use as storage biomarkers that truly reflect the cellular status at any given time during storage. Once such storage biomarkers are identified, they will be validated using the SCID mouse model.

Mission Relevance & Outcomes: Developing strategies for infectious agent interventions and identification of storage biomarkers for blood cells and related products are two unmet needs in transfusion medicine today. The outcome of the research approach outlined above has therefore high relevance to the mission of OBRR, CBER. It is anticipated that successful completion of these two research projects will enhance the safety of blood, blood components and related products.

---

Publications

Arch Virol 2008;153(12):2283-90
Defective rotavirus particle assembly in lovastatin-treated MA104 cells.
Mohan KV, Muller J, Atreya CD

BMC Cell Biol 2008 Apr 28;9(1):22
Application of Bioinformatics-Coupled Experimental Analysis reveals a new Transport-Competent Nuclear Localization Signal in the Nucleoprotein of an Influenza A Virus strain.
Ketha KM, Atreya CD

Biologicals 2006 Dec;34(4):265-72
Comparative molecular characterization of gene segment 11-derived NSP6 from lamb rotavirus LLR strain used as a human vaccine in China.
Mohan KV, Glass RI, Atreya CD

Arch Virol 2006 Sep;151(9):1841-51
The rubella virus nonstructural protease recognizes itself via an internal sequence present upstream of the cleavage site for trans-activity.
Chen HH, Stark CJ, Atreya CD

Virol J 2005 Apr 15;2(1):35
Molecular advances in the cell biology of SARS-CoV and current disease prevention strategies.
Stark CJ, Atreya C

Birth Defects Res A Clin Mol Teratol 2004 Jul;70(7):431-437.
Rubella Virus and Birth Defects: Molecular Insights into the Viral Teratogenesis at the Cellular Level
Atreya CD, Mohan KV, Kulkarni S.

Arch Virol 2004 Apr;149(4):779-89
Rubella virus P90 associates with the cytokinesis regulatory protein Citron-K kinase and the viral infection and constitutive expression of P90 protein both induce cell cycle arrest following S phase in cell culture.
Atreya CD, Kulkarni S, Mohan KV