Structural studies of viral replication and invasion

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Principal Investigator: Hideki  Aihara
Organization: UNIVERSITY OF MINNESOTA
Fiscal Year: 2024
Award: $619,646
Funding agency: National Institute of General Medical Sciences

Abstract
Viruses are a major threat to human health. Our laboratory uses various structural biology techniques to
dissect molecular mechanisms of how viruses replicate and invade the host cell or its genome. One area of our
major interest is retroviral integration, a critical step in the lifecycle of retroviruses that achieves permanent
insertion of the reverse-transcribed viral genome into a host chromosome. We will build on our recent structural
studies of the Human T-cell Leukemia virus and Rous sarcoma virus intasomes and further investigate the
roles of host factors during integration of these retroviruses. Another area that we are pursuing is the
replication of coronavirus RNA genomes and host cell invasion. In particular, we are interested in how a virally
encoded exoribonuclease complex facilitates faithful replication of the large RNA genomes of coronaviruses,
and how this unique proofreading activity could be modulated by small molecules. We are also investigating
inhibition of the receptor binding of the coronavirus spike protein by novel antibodies and antibody-mimics.
Overall, the studies proposed in this application will help better understand important RNA-based human
pathogens and could aid in the development of antiviral strategies, or alternatively, gene delivery tools useful in
research or gene therapy applications.

Terms: <Antibodies><Area><Cancers><Cell Body><Cells><Chromosomes><CoV S protein><CoV glycoprotein S><CoV spike glycoprotein><CoV spike protein><Complex><Coronaviridae><Coronavirus><Coronavirus glycoprotein S><Coronavirus spike protein><DNA Therapy><Development><Exoribonucleases><Gene Delivery><Gene Transfer Clinical><Genetic Intervention><Genome><Goals><HTLV Viruses><HTLV group><Health><Host Factor><Host Factor Protein><Human><Human T-Cell Leukemia Viruses><Human T-Cell Leukemia-Lymphoma Viruses><Human T-lymphotropic Viruses><Integration Host Factors><Invaded><Laboratories><Life Cycle><Life Cycle Stages><Malignant Neoplasms><Malignant Tumor><Modern Man><Molecular><Non-Polyadenylated RNA><RNA><RNA Gene Products><Receptor Inhibition><Research><Retroviridae><Retroviruses><Ribonucleic Acid><Role><Rous sarcoma virus><Techniques><Viral><Viral Genome><Viral Reverse Transcription><Virus><Virus Replication><Virus-Retrovirus><anti-viral development><anti-viral drug development><anti-viral therapeutic development><anti-viral therapy development><antiviral development><antiviral drug development><antiviral therapeutic development><antiviral therapy development><corona virus><coronavirus S protein><coronavirus spike glycoprotein><developing anti-viral agent><developing anti-viral drug><developing anti-viral therapeutic><developing anti-viral therapy><developing antiviral agent><developing antiviral drug><developing antiviral therapeutic><developing antiviral therapy><developmental><gene repair therapy><gene therapy><gene-based therapy><genetic therapy><genomic therapy><human pathogen><interest><life course><malignancy><neoplasm/cancer><novel><receptor binding><receptor bound><small molecule><social role><structural biology><tool><viral multiplication><viral replication><virus genome><virus multiplication>