New Genetic Tools for Comparative Analysis of Emerging Viruses and Virus-Host Molecular Interactions in Reservoir Hosts Versus Spillover Hosts
Abstract
Emerging viruses are viruses that spillover from other animals (reservoirs) into human populations, and in some cases, may be undergoing a process of adapting to humans as “new” hosts. Emerging viruses are associated with severe pathogenesis and increased death rates -- examples include HIV-1/HIV-2, Zika virus, the Middle East Respiratory Syndrome Coronavirus (MERS CoV), SARS-CoV, Ebolavirus, and the highly pathogenic Avian influenza viruses, just to name a few. For a variety of reasons, emerging viruses pose significant problems for military personnel living in close quarters, and/or deployed overseas (where exposure to novel viruses often occurs), and are of concern due to the potential use of emerging viruses as bioweapons and bioterrorism agents. While extensive efforts have done into epidemiological surveys and forecasting models, there remains a glaring gap in our understanding of the molecular mechanisms of viral emergence, and, in particular, why some viruses fail to emerge, others jump into humans and cause disease but fail to spread, and others successfully spread and adapt to humans. Work on such issues is largely focused on individual viruses and their replication in humans and human cell lines and is not focused on developing a theoretical framework and discovering “rules” that underlie the biology of emerging viruses. This gap in knowledge could be filled by taking comparative approaches, examining the same virus (or related viruses) in reservoir hosts versus spillover hosts (i.e., humans) in order to (1) identify the virus-host molecular interactions that differ between the two contexts and (2) identify genetic barriers that drive adaptation of emerging viruses to replication in human cells and tissues. In order to identify such interactions at the level of protein-protein interactions, we propose to use a cutting-edge approach that allows the modification of viral proteins in such a way that facilitates our ability to “capture” the cellular proteins that are bound or degraded by certain viral proteins, as a first step towards understanding how these viral proteins help emerging viruses adapt to new hosts. For the purposes of this Discovery Award proposal, we have made the practical choice to focus on two specific viruses, the primate immunodeficiency viruses (e.g., HIV-1) and a much more recently discovered virus, the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). While this allows us to focus our efforts during the short period of support (18 months), the overarching goal is to spark the discovery of key virus-host interactions that have the greatest impact on whether viruses successfully spillover into humans and to seek fundamental principles that could apply to a wide range of current and future emerging viral diseases.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810051
Entities
People
- Welkin E Johnson
Organizations
- Boston College
- United States Army