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MOLECULAR BIOLOGY OF RUBELLA VIRUS

Award Number: R01AI021389
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: HEALTH SERVICES
PERIOD OF PERFORMANCE START DATE: 07/01/1984
PERIOD OF PERFORMANCE END DATE: 03/31/2007

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MOLECULAR BIOLOGY OF RUBELLA VIRUS - DESCRIPTION (provided by applicant): Rubella virus (RUB), the sole member of the Rubivirus genus in the Togavirus family of RNA viruses, is a major human pathogen that is the most potent teratogen of an infectious nature. Use of live, attenuated vaccines control rubella, however these vaccines have been associated with arthritis in adult women and placental transfer to the fetus, contraindicating vaccination during pregnancy. The proposed research will continue a long-term study of the molecular biology of RUB aimed at understanding virus pathogenesis and evolution. The focus of study is the RUB nonstructural proteins (NSP's) involved in virus RNA replication. The NSP's have been implicated in RUB-induced pathogenesis and are of evolutionary interest in that, by computer alignment, they are more closely related to hepatitis E virus (HEV, an unclassified enteric virus) than to the alphaviruses, the other Togavirus genus. The first specific aim is to study domains of the RUB NSP's that are unique to RUB. The structure of two Zn binding domains within the protease that processes the NSP's from a precursor will be analyzed (hypothesis: the RUB protease is a metalloprotease, a type of protease not previously found in RNA viruses). Another putative Zn binding motif in the RUB NSP's will be analyzed (hypothesis: the Zn domain participates in methyltransferase activity). Finally, the function of a recently discovered domain that can be complemented by the virus capsid gene will be studied (hypothesis: complementation is at the RNA level). In the second specific aim, the effect of precursor processing on the structure of the NSP complex will be analyzed. The NSP's of plus-strand RNA viruses are multifunctional proteins and the impact of processing on these proteins, which function in a complex, is not understood. RUB produces two NSP's by a single cleavage of the precursor (other viruses produce four or more NSP's) and advantage will be taken of this minimal number of proteins to analyze the effect of cleavage on subsequent interaction of the NSP's. Binding sites between the NSP's will be mapped and the effect of independent expression and insertion of additional cleavage sites will be explored (hypothesis: complex formation is not dependent on initial synthesis as a precursor). Additionally, in vitro expression of the HEV NSP's will be used to determine how many NSP's are produced (hypothesis: HEV produces two NSP's confirming relatedness with RUB previously indicated only by computer).


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: 2006 ( Subtotal = $366,768 )
2006	2006	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION	33 GILMER STREET SOUTHEAST	ATLANTA	GA	30303	FULTON	USA	Allergy and Infectious Diseases Research	000	20	3/20/2006	NON-COMPETING CONTINUATION	$366,768
														Subtotal = $366,768

Issue Date FY: 2005 ( Subtotal = $376,409 )
2005	2005	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION	33 GILMER STREET SOUTHEAST	ATLANTA	GA	30303	FULTON	USA	Microbiology and Infectious Diseases Research	000	19	3/28/2005	NON-COMPETING CONTINUATION	$376,409
														Subtotal = $376,409

Issue Date FY: 2004 ( Subtotal = $369,628 )
2004	2004	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION	PO BOX 4030	ATLANTA	GA	30302	FULTON	USA	Microbiology and Infectious Diseases Research	001	18	4/30/2004	SUPPLEMENT FOR EXPANSION	$42,253
2004	2004	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION	PO BOX 4030	ATLANTA	GA	30302	FULTON	USA	Microbiology and Infectious Diseases Research	000	18	3/10/2004	NON-COMPETING CONTINUATION	$327,375
														Subtotal = $369,628

Issue Date FY: 2003 ( Subtotal = $327,375 )
2003	2003	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION	PO BOX 4030	ATLANTA	GA	30302	FULTON	USA	Microbiology and Infectious Diseases Research	000	17		COMPETING CONTINUATION	$327,375
														Subtotal = $327,375

Issue Date FY: 2000 ( Subtotal = $290,005 )
2000	2000	GEORGIA STATE UNIVERSITY	PO BOX 4030	ATLANTA	GA	30302	FULTON	USA	Microbiology and Infectious Diseases Research	000	16	6/8/2000	NON-COMPETING CONTINUATION	$290,005
														Subtotal = $290,005

Issue Date FY: 1999 ( Subtotal = $287,244 )
1999	1999	GEORGIA STATE UNIVERSITY	PO BOX 4030	ATLANTA	GA	30302	FULTON	USA	Microbiology and Infectious Diseases Research	000	15	6/28/1999	NON-COMPETING CONTINUATION	$219,388
1999	1999	GEORGIA STATE UNIVERSITY	PO BOX 4030	ATLANTA	GA	30302	FULTON	USA	Microbiology and Infectious Diseases Research	001	15	9/24/1999	SUPPLEMENT FOR EXPANSION	$67,856
														Subtotal = $287,244

Issue Date FY: 1998 ( Subtotal = $211,967 )
1998	1998	GEORGIA STATE UNIVERSITY	PO BOX 4030	ATLANTA	GA	30302	FULTON	USA	Microbiology and Infectious Diseases Research	000	14	5/29/1998	NON-COMPETING CONTINUATION	$211,967
														Subtotal = $211,967

Grand Total All Awards = $2,229,396

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MOLECULAR BIOLOGY OF RUBELLA VIRUS

Award Number: R01AI021389

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: HEALTH SERVICES

PERIOD OF PERFORMANCE START DATE: 07/01/1984

PERIOD OF PERFORMANCE END DATE: 03/31/2007

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