Role of Lipids Reorganized by Viral Proteins and Restriction Factors in Viral Life Cycle
Abstract
This Savannah State University (SSU) proposal aims to identify the interaction of lipids, viral accessory proteins, and host restriction factors, which will provide new insights and knowledge on the fundamental aspects of innate immunity and on host-virus coevolution. As a consequence of the continuous arms race between hosts and viruses, both hosts and viruses show signatures of adoption in their genome. While hosts have developed restriction factors that are proteins limiting viral replication in the infected cells, some viruses have acquired their own accessory proteins to counteract host restriction factors. The significance of cellular lipids in viral replication has been recognized. Especially, it is important for enveloped viruses since infection of many pathogenic viruses require viral envelopes that are derived from host cell membranes. Although host restriction factors, viral proteins and lipids change viral assembly, release and infectivity, mechanisms and roles of the lipid molecules and their metabolic pathways reorganized by viral accessory proteins and restriction factors remain elusive, and this gap needs to be addressed. Our long term goal is to discover novel functions of hosts/viral proteins and lipids, and clarify how they regulate viral replication at the cellular and organismal levels. The overall objective here is to identify lipid synthesis pathways affected by host restriction factors and retroviral accessory proteins, and to clarify their roles in several viral replications. Our central hypothesis is that viral accessory proteins will interact with cellular proteins including restriction factors and could change lipid metabolisms and trafficking of proteins/lipids in cells, which facilitates viral replication. Of note, we and others recently found significance of retrovirus-ganglioside interaction in viral replication. We plan to test our central hypothesis and will accomplish our objective for this project by completing two aims/steps. The first step of the project will establish a model system to investigate host-viral interaction by clarifying reciprocal interaction of restriction factors, retroviral accessory proteins and ganglioside synthesis pathways. The second step will expand the targets from gangliosides to a wide range of molecules relevant to lipid metabolism, and will clarify roles of the identified lipid molecules in viral replication. Our expected outcomes in the proposed project are to identify lipid molecules modulated by restriction factors and viral proteins, and to determine their roles in virus replication. Regardless of different pathogenic outcomes, many viruses share basic systems in replication. Such results are expected to advance our knowledge of host-virus interaction among different viruses, and to provide deep insights about how viruses have evolved in hosts. We believe that our proposal will contribute to the DoD mission because it will substantially enhance understanding in molecular genetics, immunology and virology, which could contribute to development of medical countermeasures (e.g., gene therapies, vaccines, viral strain selections) that will protect both military and civilian personnel from virus-based bioweapons, traditional viruses, and virus associated diseases (e.g., AIDS, flu, respiratory syndrome, hemorrhagic fevers). The research project will support SSU (84% African American enrollment) underrepresented minority (URM) students to pursue STEM research careers including in DoD mission areas through financial support and hands-on training using state-of-the-art instruments and techniques in molecular biology, and will develop the next generation URM STEM workforce in the USA. The information of the project will be disseminated to the local community through the university website, Facebook, the university newspapers, local community forums and journals.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Feb 19, 2019
- Source ID
- W911NF1810405
Entities
People
- Takayuki Nitta
Organizations
- Army Contracting Command
- Office of the Secretary of Defense
- Savannah State University