The human virome is defined as a collection of all viruses that are found in or on humans, including both eukaryotic and prokaryotic (bacteriophages) viruses and viral particles. Excluding the relatively small number of viruses that are the causative agents of some clinical diseases, the virome is largely understudied and its molecular interactions within the human host remain mostly uncharacterized. Whether and how virome composition and interactions impact human health remains largely unknown.

The overall goal of the Human Virome Program (HVP) is to characterize the human virome, including eukaryotic and prokaryotic viruses and viral particles. The HVP will also create tools, models, and methods that will enable in-depth study of the virome’s breadth and variation, its association with host factors and its influence on human health. It is anticipated that exploration of the human virome will provide insights into the health effects of inter-kingdom interactions (host-virome and microbiome-virome) occurring within the human body and inform future studies examining novel connections with human health. The HVP consists of four initiatives that work synergistically to achieve the goals of the program. These initiatives are:

1. Characterizing the human virome and its dynamics by utilizing longitudinal, demographically diverse (i.e., age, sex, race, ethnicity, etc.) human cohorts.
2. Facilitating the discovery and annotation of viruses by developing tools, models, and methods that will improve detection, sensitivity, purification, and scalability.
3. Studying interactions between the virome and the human host, as well as with other components of the human microbiome.
4. Creating a Consortium Organization and Data Collaboration Center (CODCC) that will serve as an organizational and cooperation hub for the HVP Consortium and external groups and through the creation of a human virome catalog and data portal.

Outcomes from the HVP will be foundational for building a human virome atlas and translating new knowledge into the discovery of novel health-related biomarkers.

This program is funded through the NIH Common Fund as a short-term, goal-driven strategic investment, with deliverables intended to catalyze research across multiple biomedical research disciplines. The NIH Common Fund supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives are expected to support the development of bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.

Research Objectives and Scope

Advances in metagenomic sequencing and bioinformatic innovations provide an unprecedented opportunity to characterize the human virome and its host dynamics across- and impact on- heterogeneous human cohorts and tissue types.

The objective of this funding opportunity is to expand, complement, or improve existing tools and models and those developed from the HVP through pilot projects that harmonize with the goals of the HVP, such as:

• Projects proposing the use of biospecimens should strive to have cohorts with an absence of overt disease (consider physiological and mental well-being). The cohorts, sampling sites, and biospecimens will be assessed programmatically to prevent over-representation of certain conditions and to ensure that participants are aligned with the average health of the U.S. population.
• Projects addressing the technological and methodological challenges currently hindering robust interrogation of the constituents and functionality of the human virome should focus on 1) complementing the development of existing innovative and novel tools, models, and methods which overcome the major challenges in identifying and characterizing human viruses, including computational biology and bioinformatics tools to enhance the analysis and visualization of the human virome. Projects cannot overlap with existing HVP efforts and should not focus on specific disease states.
• Projects focused on characterizing the functional interactions between the virome, microbiota (bacteria, archea, fungi), and human host may propose a range of studies, including (but not limited to) virome/virus basic biology, virus-bacteria, virus-fungi and virus-host interactions; detailed studies of single or multiple virome members; comparative virome investigations; and/or studies of viromes from multiple sites of the body. All prokaryotic and eukaryotic viruses are of interest; however, studies must involve the human host and clearly lead to a better understanding of the human host/virome symbiosis and inter-kingdom relationships.