XMRV & CFS -Relationship Functional Status & Co-Infections -NIH

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Project Information

DESCRIPTION

Project Number: 1R21AI090553-01

Contact Principal Investigator:

HANSON, MAUREEN REBECCA

Title:

THE RELATIONSHIP OF XMRV

TO FUNCTIONAL STATUS AND

CO-INFECTIONS IN CHRONIC

FATIGUE

Awardee Organization:

CORNELL UNIVERSITY ITHACA

Abstract Text:

DESCRIPTION (provided by applicant):

Chronic fatigue syndrome (CFS) is an illness

characterized by long-term fatigue, impaired memory

or concentration, sore throat, tender lymph nodes,

muscle pain, multi-joint pain, new headaches,

unrefreshing sleep, and exercise intolerance.

While the cause(s) of chronic fatigue syndrome has

not been established definitively, a number of

outbreaks implicate an infectious etiology.

A variety of pathogens have been reported in

individual CFS patients or found more frequently in

CFS patients than controls, including various types of

viruses.

The immune systems of CFS patients exhibit both

chronic activation and dysfunction.

Recently, a new human retrovirus named XMRV

(Xenotropic Murine Leukemia Virus-Related Virus)

has been detected in a large proportion of CFS

patients tested, but in only 4% of healthy subjects.

We plan to learn more about the association of

XMRV and other pathogens with CFS by examining an

outbreak cohort not previously screened for the

presence of XMRV.

Other viruses, microbes, and parasites that may be

associated with XMRV will also be detected with the

use of a panmicrobial DNA microarray.

We will determine whether the presence of XMRV

and/or other pathogens is related to the current

state of health of individuals who became ill during a

1985 outbreak in rural New York.

Assuming that most members of the New York cohort

are infected with XMRV, we will amplify and

sequence XMRV envelope genes derived from blood

cells of 40 individuals who became ill as children in

1985.

We will also sequence envelope genes from 80

subjects in the Nevada cohort known to exhibit a

high degree of XMRV infection.

We will examine phylogenetic relationships between

the Nevada and New York XMRV variants and will

observe whether any amino acid substitutions

correlate with the current state of health of the

subjects.

We will also study the possible association of XMRV

and XMRV protein expression in the phenomenon of

exercise intolerance.

We will examine XMRV-infected CFS patients before

and after an exacerbation of symptoms caused by

serial exercise testing.

We will determine whether increases in inflammatory

cytokines, a growth factor, and nitric oxide, or blood

cell changes are correlated with the extent of

reduced physical ability that can be measured during

a second exercise test taken after induction of

postexertional malaise.

All of these experiments will be designed to assess

whether particular XMRV sequences and expression

levels play a role in the symptoms experienced by

CFS patients and to detect possible underlying

mechanisms of the disability that impairs their

physical activity.

PUBLIC HEALTH RELEVANCE:

Chronic fatigue syndrome, an illness that disables

many Americans, has recently been associated with

the presence of a new human retrovirus.

We will investigate whether this retrovirus is both

necessary and sufficient for the development of the

illness, or whether additional pathogens are

involved.

We will determine whether the level of health and

exercise intolerance in chronic fatigue syndrome is

related to particular virus variants, expression of

viral proteins, and/or dysfunction of the immune

system.

NIH Spending Category:

Cardiovascular; Chronic Fatigue Syndrome (ME/CFS);

Clinical Research; Health Disparities; Infectious

Diseases; Prevention; Rural Health

Project Terms:

0-11 years old; Aching muscles; Aerobic Activity;

Aerobic Exercise; American; Amino Acid Substitution;

Anaerobic Threshold; Antibodies; Arthralgia;

Autonomic nervous system; Bacteria; bacterial

disease; Bacterial Infections; Blood; Blood Cell

Count; Blood Cell Number; Blood Cells; body system,

allergic/immunologic; Causality; Cells; Cephalalgia;

Cephalgia; Cephalodynia; Cephalodynias; Child;

Child Youth; Childhood; children; Children (0-21);

Chronic; Chronic Fatigue and Immune Dysfunction

Syndrome; Chronic Fatigue Disorder; Chronic Fatigue

Syndrome; Chronic Fatigue-Fibromyalgia Syndrome;

coat (enveloped virus); cohort; Cranial Pain;

cytokine; design; designing; Development; disability;

disease causation; disease etiology; Disease

Outbreaks; disease/disorder etiology; disorder

etiology; DNA Chips; DNA Microarray; DNA Microarray

Chip; DNA Microchips; Dysfunction;

Encephalomyelitis, Myalgic; Endogenous Nitrate

Vasodilator; endothelial cell derived relaxing factor;

Endothelium-Derived Relaxing Factor; Etiology;

Exercise; Exercise stress test; Exercise Test;

Exercise, Physical; Exhibits; experience; experiment;

experimental research; experimental study; Fatigue;

Functional disorder; functional status;

Gammaretrovirus; Genes; GFAC; Growth Agents;

Growth Factor; Growth Factors, Proteins; Growth

Substances; HBLV; Head Pain; Headache; Health;

Health Status; Herpesvirus 6, Human; HHV-6; HHV6;

Human; Human B-Lymphotropic Virus; Human

Herpesvirus 6; Human, Child; Human, General;

Immune; Immune system; Immune System and

Related Disorders; Immune System Dysfunction;

Immunodeficiency and Immunosuppression

Disorders; Immunological Dysfunction;

Immunological System Dysfunction; Individual;

Infection; Infectious Mononucleosis-Like Syndrome,

Chronic; Inflammatory; Joint Pain; Lack of Energy;

Learning; Level of Health; Location; loss of function;

lymph gland; Lymph node proper; lymph nodes;

Malaise; mammalian type C retrovirus group; Man

(Taxonomy); Man, Modern; Measurement; Measures;

member; Memory; Methods; Microbe; Monitor;

Mononitrogen Monoxide; Morphology; Mouse

Leukemia Viruses; Murine leukemia virus; Muscle

discomfort; Muscle pain; Muscle pain/fibrositis;

Muscle sorenesss; Myalgia; Myalgia unspecified;

Myalgic; Myodynia; Myoneuralgia; Myosalgia; Names;

Nevada; New York; Nitric Oxide; Nitric Oxide,

Endothelium-Derived; Nitrogen Monoxide; Nitrogen

oxide; Nitrogen Protoxide; Nucleic Acids; organ

system, allergic/immunologic; Outbreaks; Oxygen

Consumption; Parasites; pathogen; pathophysiology;

patient population; Patients; pediatric; Performance;

Peripheral Blood Cell; Phylogenetic Analysis;

Phylogenetics; Physical activity; Physiologic;

Physiological; Physiopathology; Play; Postviral

Fatigue Syndrome; prevent; preventing; Production;

protein expression; Proviruses; public health

relevance; Reporting; research study;

Reticuloendothelial System, Blood;

Reticuloendothelial System, Lymph Node;

Retroviridae; Retroviruses; Role; Royal Free Disease;

Rural; Sampling; Sleep; social role; Sore Throat;

Symptoms; Testing; Type C Retroviruses,

Mammalian; Variant; Variation; Vascular Endothelial

Growth Factors; Vegf; VEGFs; Viral; Viral Diseases;

Viral Gene Products; Viral Gene Proteins; viral

infection; Viral Proteins; Virus; Virus Diseases; virus

envelope; virus infection; virus protein; Virus-HHV6;

Virus-Retrovirus; Viruses, General; youngster

DETAILS

Project Number: 1R21AI090553-01

Contact Principal Investigator: HANSON, MAUREEN

REBECCA

Title: THE RELATIONSHIP OF XMRV TO FUNCTIONAL

STATUS AND CO-INFECTIONS IN CHRONIC FATIGUE

Awardee Organization: CORNELL UNIVERSITY

ITHACA

Contact PI Information:

Name: HANSON, MAUREEN REBECCA Add Profile

Email: mrh5@...

Title: LIBERTY HYDE BAILEY PROFESSOR

Program Official Information:

Name: PARK, EUN-CHUNG

Email: epark@...

Organization:

Name: CORNELL UNIVERSITY ITHACA

City: ITHACACountry: UNITED STATES (US)

Department/ Educational Institution Type:

BIOCHEMISTRY

EARTH SCIENCES/RESOURCES

Congressional District:

State Code: NY

District: 22

Other Information:

RFA/PA: PA-08-247

Study Section: Special Emphasis Panel (ZRG1)

Fiscal Year: 2010 Award Notice Date:

8-JUN-2010

DUNS Number: 872612445

Project Start Date: 15-JUN-2010

Budget Start Date: 15-JUN-2010

Budget End Date: 31-MAY-2011

CFDA Code: 855

Administering Institutes or Centers:

NATIONAL INSTITUTE OF ALLERGY

AND INFECTIOUS DISEASES

Project Funding Information for 2010:

Total Funding: $269,496