R01AI188432

DECIPHERING THE ROLE OF CHEMOKINE RECEPTOR CCR5 IN MATERNAL FLAVIVIRUS INFECTIONS - PROJECT SUMMARY: CCR5 IS A CHEMOKINE RECEPTOR INVOLVED IN LEUKOCYTE TRAFFICKING. WE IDENTIFIED A NEUROPROTECTIVE ROLE FOR CCR5 IN THE CONTEXT OF WEST NILE VIRUS (WNV) INFECTION BOTH IN MICE AND HUMANS. IN MICE, WE FOUND THAT MICE LACKING CCR5 ARE SIGNIFICANTLY MORE SUSCEPTIBLE TO WNV-INDUCED ENCEPHALITIS COMPARED TO WILD TYPE (WT) MICE. WE TRANSLATED THESE RESULTS USING HUMAN COHORTS, WHERE WE FOUND THAT INDIVIDUALS THAT NATURALLY LACK CCR5 (CCR5∆32 HOMOZYGOTES) DEVELOP MORE SEVERE SYMPTOMS FOLLOWING INFECTION WITH WNV. FURTHERMORE, WE AND OTHERS HAVE SHOWN THAT THIS PROTECTIVE EFFECT WAS NOT LIMITED TO WNV INFECTION, BUT THAT THE LOSS OF CCR5 INCREASED SUSCEPTIBILITY TO NUMEROUS OTHER NEUROTROPIC FLAVIVIRUSES, INCLUDING TICK-BORNE ENCEPHALITIS VIRUS (TBEV), AND JAPANESE ENCEPHALITIS VIRUS (JEV). ZIKV IS OF PARTICULAR CONCERN BECAUSE OF ITS IMPACT ON PREGNANCY, WITH MICROCEPHALY AND OTHER CONGENITAL MALFORMATIONS, AS WELL AS FETAL LOSS, STILLBIRTH, AND PRETERM BIRTH AMONG THE POSSIBLE OUTCOMES. IN PRELIMINARY DATA, WE FOUND THAT THE LOSS OF CCR5 INCREASES SUSCEPTIBILITY TO ZIKV (A KNOWN TERATOGEN) DURING MATERNAL INFECTIONS, RESULTING IN POOR PREGNANCY OUTCOMES. THIS WAS ALSO TRUE FOR WNV, A VIRUS NOT KNOWN TO IMPACT PREGNANCY. IN THIS APPLICATION, WE WILL TEST THE HYPOTHESIZE THAT CCR5 IS PROTECTIVE AGAINST FLAVIVIRUS-INDUCED CONGENITAL DISEASE. THIS APPLICATION WILL UNRAVEL THE MECHANISMS INVOLVED IN CCR5-MEDIATED PROTECTION DURING MATERNAL FLAVIVIRUS INFECTIONS.

Icahn School Of Medicine At Mount Sinai

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

New York United States

State-Wide

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)