Key Dates

Related Announcements

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Issued by

Office of Strategic Coordination (Common Fund)

Purpose

The purpose of this Request for Information (RFI) is to solicit information from the broad community about opportunities and challenges in elucidating the human virome.

Background

Viruses are the most abundant and diverse biological entities on earth. The human virome is similarly large and diverse, with as many as 10¹³ particles per human. Excluding the relatively small number of viruses that cause obvious clinical disease through human infection, viruses are largely understudied. Opportunities to study the human virome composition and diversity, variability over time, viral host cells, longitudinal impact on human health, and the influence of environment are needed.

Humans are rapidly colonized by viruses after birth, and evidence suggests that the virome may remain fairly stable throughout life while showing great interindividual variability.¹ Most virome studies are small with cohorts of hundreds (with few studies in the thousands) and can suffer from inter-study variability from technical artifacts that can drown out disease effects at the population level. And while methods exist to quantify exposure to an array of viruses, most miss much of the human virome. Assessing the full viral population will require physical isolation of viral particles from specimens of interest and sequencing purified particles from a large enough cohort to capture viral diversity. Assessing associations of the virome with human and other microbial hosts will similarly require large and focused cohorts.

With the decreasing costs of metagenomic sequencing, cloud computing, and broad serologic viral assays, the potential for systematic longitudinal virome assessments is promising and feasible in a way that was previously impossible. The virome is incredibly diverse and the majority of viral sequences do not align to known sequences in existing databases (known as viral “dark matter”) and that composition is highly unique to individuals. Virome assessment would benefit from both technological innovation/development of better assays to assess the viral “dark matter” as well as larger and broader longitudinal studies in diverse populations to determine the range, evolution, microbiome interaction, and clinical impact of the virome. Human studies could incorporate virome assessment with human genomics, multi-omics analysis of the full microbiome, and longitudinal clinical outcomes. Viromes could be obtained from different physiological samples, including from saliva, intestinal contents, blood, cervico-vaginal secretions, and the throat/nose.

In order to help identify the needs and priorities in this area of science, and plan future activities and initiatives that can most significantly impact biomedical research, the Human Virome Working Group of the NIH Common Fund is seeking comments from the global community regarding conceptual, technical and/or methodological barriers that are currently limiting progress in this field and to help prioritize research activities or community resources that are most likely to propel this field forward for the greater benefit of the biomedical research community.

Information Requested

The NIH is considering the possibility of developing a Common Fund program to better understand the human virome. As part of the initial planning process, we are requesting input from the scientific community on the current challenges in this field that can best be addressed through a concerted and coordinated effort. This RFI seeks input from stakeholders throughout the scientific research community and the public regarding any of the following topics, as well as any additional ideas not included below:

1. Research to define and characterize the human virome
2. Research to understand the establishment of the human virome in the neonatal period, through infancy, and into early childhood
3. Research to understand how the different parts of the human virome (e.g., eukaryotic and prokaryotic, and between different body sites) interact
4. Research to understand how the virome interacts with the other parts of the microbiome
5. Research to understand the impact of commensal eukaryotic viruses and bacteriophages on the human immune system and pathogenicity and virulence of other viruses
6. Methods, tools, or resources needed for the research outlined above, particularly:
   1. VirScan and other serological assays
   2. Viral particle isolation from different biological specimens
   3. Metagenomic sequencing and coverage of virome
   4. Bioinformatic tools for metagenomic and “dark matter” data analysis
   5. Clinical Panels
   6. Methods of data standardization and cross-study comparison
7. Specific populations for whom research on the human virome should be prioritized (and a rationale for the proposed priorities)
8. Characterization of particular challenges, acceptability, and feasibility of obtaining biospecimens/tissue samples and other clinical and environmental measures
9. Resources (e.g., biorepositories, registries, and electronic health records) that could be leveraged or used to advance human virome research

How to Submit a Response

Responses to this RFI will be accepted through April 29, 2022. All comments will be anonymous and must be submitted via email to HumanVirome@od.nih.gov. Please include the Notice number (NOT-RM-22-010) in the subject line.

In your email, please include the bullet you are addressing (or if you are proposing a novel topic), and justification for your suggestion. Please note that we are interested in addressing both challenges and opportunities in the human virome field that, if addressed, would significantly move the field forward.

The Common Fund will hold a public workshop discussing the human virome concept on April 29, 2022, from 1-5 p.m. EDT. The workshop will hold sessions around three main concepts with discussion from invited panelists and moderators. The concepts are:

1. Defining and characterizing the human virome in different tissue compartments in diverse populations across the lifespan.
2. Outlining the establishment of the human virome in the neonatal period, through infancy, and into early childhood
3. Describing relevant, diverse disease cohorts with appropriate longitudinal samples and clinical data available for the analysis of potential virome/microbiome associations with disease.

The workshop is open to the public. Those who require reasonable accommodations for this event should contact organizers at HumanVirome@od.nih.gov by April 22, 2022. Go to https://commonfund.nih.gov/humanvirome/workshop to learn more about the workshop and how to join.

Responses to this RFI are voluntary. The Government is under no obligation to acknowledge receipt of the information provided and respondents will not receive individualized feedback. This RFI is for planning purposes only and should not be construed as a solicitation or as an obligation on the part of the United States Government. NIH will use the information submitted in response to this RFI at its discretion. NIH does not intend to make any type of award based on responses to this RFI or to pay for either the preparation of information submitted or the United States Government's use of such information. The information submitted will be analyzed and may be shared internally, appear in reports or be reflected in future solicitations, as appropriate and at the Government's discretion. Proprietary, classified, confidential, or sensitive information should not be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s) or other activities. No basis for claims against the U.S. Government shall arise as a result of a response to this request for information or from the Government's use of such information.

Reference

1. Liang, G., and Bushman, F.D. (2021). The human virome: assembly, composition and host interactions. Nat. Rev. Microbiol. 19, 514–527.

Inquiries

Please direct all inquiries to:

Leia Novak, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Te301-761-7825
HumanVirome@od.nih.gov

Stacy Carrington-Lawrence, Ph.D.
National Institute on Aging (NIA)
301-496-6402
HumanVirome@od.nih.gov