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Principal Investigator: Junki Maruyama
Organization: UNIVERSITY OF TEXAS MED BR GALVESTON
Fiscal Year: 2022
Award: $63,240
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT
This career development award will help fill in the knowledge and skills in basic virological research of Risk
Group 4 agents, which need to be handled in the highest containment laboratory (BSL-4). This is essential for
the goal to become an independent researcher as an expert on highly pathogenic infectious diseases. The goal
during the award period is to reveal novel mechanisms of Lassa fever (LF) by using both in vivo and in vitro
techniques, leading to new insight into the development of countermeasures and controlling methods against
Lassa fever.
Lassa virus (LASV) is endemic in West African countries and causes outbreaks of LF annually. Although LASV
is one of the most alarming pathogens from a public health perspective, there are few effective vaccines or
therapeutics against LF. LASV must be handled at biosafety level 4 (BSL-4), due to its high pathogenicity. This
is one of the largest barriers to the development of preventive or therapeutic approaches against LF. Furthermore,
animal models of LF are limited, which is essential for basic research and development of countermeasures.
Recently, we developed a novel guinea pig model of LF and found that LASV strain LF2384 and LF2350 have
completely different pathogenic phenotypes in guinea pigs. These two viruses have been isolated from human
LF patients and pathogenicity of these viruses in guinea pigs is consistent with human cases. These unique
combinations of immunocompetent rodent model and clinical isolated LASVs are strong tools, which allow us to
reveal viral factors responsible for pathogenicity and molecular mechanisms underlying LASV pathogenicity. In
the proposed study, we will determine factors responsible for LASV pathogenicity and reveal novel molecular
mechanisms underlying LASV infection by using reverse genetics, in vivo experiments, and several in vitro
molecular techniques.
We will address this goal through three specific aims. In Specific Aim 1, we will reveal the pathophysiology of
LASV infection in guinea pigs. In Specific Aim 2, we will determine viral factors responsible for LASV
pathogenicity by using reverse genetics and in vivo study. In Specific Aim 3, we will unveil molecular mechanisms
underlying LASV pathogenicity. Taken together, we hope to address novel pathogenic mechanisms of LASV
infection, leading to new insights to develop countermeasures against LF.
Terms: <Acute><Address><Africa><African><Animal Model><Animal Models and Related Studies><Annual Reports><Arenaviridae><Arenaviridae Infections><Arenavirus><Arenavirus Infections><Arenavirus group><Award><Basic Research><Basic Science><Biologic Containment><Biological><Biological Containment><Bleeding><Blood><Blood Reticuloendothelial System><Career Development Awards><Career Development Awards and Programs><Career Development Programs K-Series><Case Fatality Rates><Cavia><Clinical><Clinical Chemistry><Clinical Data><Communicable Diseases><Containment><Country><DNA Molecular Biology><Data><Development><Development and Research><Disease><Disease Outbreaks><Disorder><Dysfunction><Family member><French Guinea><Functional disorder><Glycoproteins><Goals><Gold><Guinea><Guinea Pigs><Guinea Pigs Mammals><Hematology><Hemorrhage><Histopathology><Human><Immune Evasion><Immune response><Immunochemical Immunologic><Immunocompetent><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><In Vitro><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Investigators><K-Awards><K-Series Research Career Programs><Knowledge><Laboratories><Lassa Fever><Lassa disease><Lassa fever virus><Lassa virus><Liberia><Methods><Modeling><Modern Man><Molecular><Molecular Biology><Nigeria><Nucleoproteins><Outbreaks><Pathogenesis><Pathogenicity><Pathogenicity Factors><Pathologic><Patients><Persons><Phenotype><Physiopathology><Preventive><Public Health><R & D><R&D><Recombinants><Research><Research Career Program><Research Personnel><Researchers><Risk><Rodent Model><Safety><Sensorineural Deafness><Sensorineural Hearing Loss><Sensory Hearing Loss><Sierra Leone><System><Techniques><Therapeutic><Vaccines><Viral><Viral Diseases><Viral Gene Products><Viral Gene Proteins><Viral Pathogenesis><Viral Proteins><Virulence><Virulence Factors><Virus><Virus Diseases><base><biologic><blood loss><cost><developmental><experiment><experimental research><experimental study><guinea pig model><host response><immune competent><immune system response><immunoresponse><improved><in vivo><in vivo Model><insight><model of animal><model organism><non-human primate><nonhuman primate><novel><pathogen><pathogenic virus><pathophysiology><research and development><reverse genetics><sensorineural hearing impairment><skills><tool><viral infection><viral pathogen><virus infection><virus pathogen><virus pathogenesis><virus protein><virus-induced disease>