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STRUCTURE AND FUNCTION OF THE CORONAVIRUS REPLICASE

Award Number: R01AI045798
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2001
PERIOD OF PERFORMANCE END DATE: 12/31/2005

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STRUCTURE AND FUNCTION OF THE CORONAVIRUS REPLICASE - DESCRIPTION: Coronaviruses are a family of RNA viruses that cause respiratory, gastrointestinal and neurological diseases in a variety of animals including humans. Coronavirus RNA synthesis is unusual because viral mRNAs are generated via a discontinuous mechanism during which a leader RNA and mRNA body sequence become contiguous. Furthermore, replicating viral RNAs undergo high frequency RNA recombination. To understand these unique mechanisms of viral RNA synthesis, we are characterizing the coronavirus replicase, the enzyme responsible for RNA synthesis and recombination. The corona virus replicase is synthesized as an 800 kDa polyprotein that is processed by viral proteinases. In this proposal, we will investigate how the replicase polyprotein is processed, assembled on intracellular membranes, and functions in viral RNA synthesis. We hypothesize that certain replicase products act as the scaffold for assembly of the replicase complex onto membranes, and that this assembly is essential for the generation of the functional replicase. Using a series of polyclonal antisera generated to individual replicase products, we will determine the subcellular localization of replicase products by confocal and immuno-electron microscopy. Biochemical methods and a system for the cytoplasmic expression of replicase products will be used to determine if individual replicase products act as integral membrane proteins or if their localization is dependent of other replication products. We will also use the cytoplasmic expression system to express replicase products in trans and determine if they can complement temperature sensitive mutants defective in viral RNA synthesis. These studies will provide new information of a viral replicase that mediates discontinuous mRNA synthesis and RNA recombination, events that contribute to the ability of viruses to rapidly evolve, evade the immune system and hamper vaccine development.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2005 ( Subtotal = $266,000 )
2005	2005	LOYOLA UNIVERSITY MEDICAL CENTER							Microbiology and Infectious Diseases Research	000	5	12/22/2004	NON-COMPETING CONTINUATION	$266,000
														Subtotal = $266,000

Issue Date FY: 2004 ( Subtotal = $402,937 )
2004	2004	LOYOLA UNIVERSITY MEDICAL CENTER							Microbiology and Infectious Diseases Research	000	4	1/2/2004	NON-COMPETING CONTINUATION	$402,937
														Subtotal = $402,937

Issue Date FY: 2003 ( Subtotal = $334,468 )
2003	2003	LOYOLA UNIVERSITY MEDICAL CENTER	2160 SOUTH FIRST AVENUE	MAYWOOD	IL	60153	COOK	USA	Microbiology and Infectious Diseases Research	000	3		NON-COMPETING CONTINUATION	$334,468
														Subtotal = $334,468

Issue Date FY: 2002 ( Subtotal = $266,000 )
2002	2002	LOYOLA UNIVERSITY MEDICAL CENTER	2160 SOUTH FIRST AVENUE	MAYWOOD	IL	60153	COOK	USA	Microbiology and Infectious Diseases Research	000	2	12/21/2001	NON-COMPETING CONTINUATION	$266,000
														Subtotal = $266,000

Issue Date FY: 2001 ( Subtotal = $266,000 )
2001	2001	LOYOLA UNIVERSITY MEDICAL CENTER	2160 SOUTH FIRST AVENUE	MAYWOOD	IL	60153	COOK	USA	Microbiology and Infectious Diseases Research	000	1	12/26/2000	NEW	$266,000
														Subtotal = $266,000

Grand Total All Awards = $1,535,405

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STRUCTURE AND FUNCTION OF THE CORONAVIRUS REPLICASE

Award Number: R01AI045798

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/01/2001

PERIOD OF PERFORMANCE END DATE: 12/31/2005

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