R01AI194449

Transmission dynamics and fitness of reemerging St. Louis encephalitis virus in mosquito vectors and West Nile virus naïve and immune avian reservoirs - Project summary/abstract

The flavivirus St. Louis encephalitis virus (SLEV) infects humans to cause febrile illness and rare fatal encephalitis.

In California (CA), although human SLEV cases were detected from the 1940s-2003, none were reported from 2004-2015.

Since 2015, SLEV reemerged and spread to cause more cases in CA and the western US, including in areas with concurrent West Nile virus (WNV), a related flavivirus that invaded CA in 2003 that uses the same Culex vectors and avian hosts as SLEV.

The reasons for the 11-year disappearance of SLEV from CA and its expansion since 2015 are unclear.

Spread of WNV across the US was facilitated by augmented avian infection and enhanced vector competence but no studies have assessed host or vector phenotype for reemerging SLEV.

Our genetic tracing studies show that post-2015 (contemporary) SLEV in the western US likely originated in South America and is genetically distinct from pre-2003 (historic) SLEV.

Our experimental studies show that birds inoculated with historic SLEV one month after WNV inoculation, a time when WNV neutralizing antibody titers are high, do not mount SLEV viremias, suggesting that SLEV after 2003 was displaced by extensive WNV avian herd immunity.

Antibody-mediated neutralization is a hallmark of protection from flavivirus viremia and disease and antibody therapies are used in severe human cases of WNV and SLEV.

Antibody is assumed to protect WNV immune birds from SLEV viremia and to prevent reinfection from sequential SLEV>SLEV infection but has never been experimentally confirmed.

Our preliminary data show that serum from birds inoculated with historic WNV poorly neutralize some contemporary SLEV strains in vitro.

Reduced antibody mediated cross-neutralization of contemporary SLEV by contemporary WNV could explain reemergence and persistence of SLEV in avian hosts.

Augmented avian or mosquito infection may also contribute to SLEV spread.

We observe increased infectivity of reemerging SLEV isolated in successive years since 2015 in duck embryonic fibroblast cells, but whether this pattern also manifests in avian reservoirs and in mosquito vectors is not known.

To understand drivers of reemergence, the goal of this project is to identify how changing SLEV-vector-avian host interactions and cross-protection by WNV promote SLEV reemergence.

This will be accomplished via 3 project aims:

1) Determine transmission competence and fitness of contemporary versus historic SLEV in Culex,

2) Define avian fitness, antibody kinetics, and antibody-mediated protection for contemporary versus historic SLEV, and

3) Evaluate avian cross-protection conferred by prior WNV for contemporary versus historic SLEV.

This project is significant in that it will define SLEV transmission dynamics in the context of sequential invasion and concurrent spread of 2 Culex-borne flaviviruses endemic to the US.

Davis University Of California

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]

Davis, California 95616 United States

Single Zip Code

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