A Deep Dive Into the Human Virome

We play host to vast numbers of different viruses.  

The human virome—the community of viruses that populate our bodies—is incredibly complex, formed of viruses that cause acute or persistent infections and those that co-exist with us without contributing to disease. 

We are constantly exposed to viruses, which can change the composition and abundance of the virome over time. It is also influenced by diet, age, medications, and disease. Furthermore, viruses within the virome interact with our immune system, which can have either beneficial or detrimental effects on our health. 

Despite increasing focus on the human virome, the vast majority of viruses that don’t appear to cause disease remain understudied. 

The National Institutes of Health (NIH) Human Virome Program (HVP) is an initiative focused on describing the “healthy” virome. Its goals are to identify and catalog these viruses, develop new tools and methods to study them, understand how they interact with the human body and other microbes, and make the resulting findings and data broadly accessible to researchers. 

At the American Society for Microbiology Microbe 2026, the NIH is hosting a panel discussion on the HVP. Ahead of the conference, Technology Networks spoke with some of the panelists to gain their insights on why studying the human virome is challenging, what we’ve learned so far about the impact of the virome on our health, and how work from the HVP might shape the future of healthcare.

 

Dr. Caleb Lareau is an assistant member in the Computational and Systems Biology Program at Sloan Kettering Institute. Dr. Yvonne L. Hernandez-Kapila is a professor and associate dean for research at the University of California, Los Angeles. Dr. Liliana Brown is the director of the Office of Genomics and Advanced Technologies at the National Institute of Allergy and Infectious Diseases. Dr. Becky Miller is the program leader of the Human Virome Program. 

Katie Brighton (KB): What do we currently know about how the human virome influences our health? 

Dr. Caleb Lareau (CL): Remarkably little! Despite the number of viral particles outnumbering human cells 10 to 1, we have very little understanding of how these viral populations differ in disease states. There have been case reports of diseases where the virome is altered in disease, but understanding whether this is correlative or causal is required to better understand how it impacts our health. 

Dr. Yvonne Kapila-Hernandez (YK-H): Despite estimates suggesting >380 trillion viruses reside within the body, an order of magnitude greater than the number of bacteria, the human virome remains largely unexplored.

Prior studies of the human virome have found it is vast, complex, and heterogeneous. Several key findings have emerged from initial attempts to define the virome in health and disease, including the existence of a spectrum of ecological niches that differ across the lifespan, complex interkingdom interactions between viruses and bacteria and with the host immune system, and the potential importance of commensal viruses.

Pandemics and worldwide threats over the past century have highlighted our limited knowledge of viral pathogens in the body. Moreover, knowledge of what constitutes a healthy human virome in diverse individuals across the human lifespan and healthspan is lacking, representing a considerable knowledge gap. 

Dr. Becky Miller (BM) and Dr. Liliana Brown (LB): We know that viruses are a natural part of the human microbiome—the collection of microbes that exist in and on us—and that the human virome is large and diverse.

While fewer than 500 viruses are known to cause human disease, trillions of other viruses—mostly bacteriophages that infect bacteria—are also found in our bodies.

Recent scientific studies have uncovered associations between the structure and composition of the human virome and some human illnesses, such as inflammatory bowel disease or diabetes. However, we still have many unanswered questions about how these viruses interact with our immune system, how they may support health, and under what circumstances they might contribute to disease.

The virome is increasingly recognized as an important part of human physiology, though its full impact is still being uncovered. 

KB: What are the major challenges in studying the human virome, and how do you think they might be overcome? 

CL: Viruses can take on all sorts of different shapes and sizes. Some are made up of only RNA, some only DNA, and yet others that don’t seem to code for any proteins. The sheer number and diversity of viruses make it difficult to create experimental methods to map them all.

We are overcoming this by bringing in individuals with diverse technological backgrounds spanning bacterial methods, soil viromics, and human genetics to collectively overcome these challenges.  

 

YH-K: Prior virome metagenomic sequencing studies found viral sequences that do not align with information in databases and thus represent viral “dark matter” that has yet to be defined. These knowledge gaps create a barrier to scientific progress, profoundly limiting our ability to detect and control viruses that pose threats to human populations.

The HVP aims to fill these gaps by means of defining all facets of the human virome across the life and health spans in diverse populations; employing and developing novel tools and approaches will be a key component to moving the field forward. 

BM and LB: Studying the human virome has been challenging due to its vast diversity within a single person, between body sites, and among different people and environments. Making comparisons between viromes is difficult because virus categorization is not straightforward. For example, viral genomes can be made up of DNA or RNA, their genome sizes can range from a few to hundreds of kilobases, their shapes can be wildly different from small spherical conformations to having complex structures, and their lifecycles are incredibly diverse. This diversity, in turn, poses challenges to developing sampling, processing, and sequencing methods that consistently identify all types of viruses.

Because of the large variety, most of the genome content of newly discovered viruses do not align with any information in existing databases, so arriving at conclusions about viral functions is extremely difficult. 

Additional challenges include distinguishing true viral signals from contamination. The HVP is designed to address these barriers by developing innovative tools, models, and computational methods, as well as building standardized datasets, protocols, and resources to support the broader research community. 

KB: Which research areas covered by the HVP are you most excited about? 

CL: Our group focuses on understanding how human cells interact with viruses. We’re particularly excited about answering how differences between humans in their immune function interact with different viruses to result in distinct health outcomes. I think that understanding how our immune system interacts with these viruses could be the key to understanding long-term immune function and potential therapeutic targets (i.e., new immunotherapies) to treat diseases beyond infections. 

YH-K: Our center at UCLA is focused on defining the viruses across the oral–gut–brain axis; an important functional unit already known to exist and with relevance to the human microbiome in health and disease. 

BM and LB: The program spans several important areas, including large-scale characterization of the human virome from people in the US, development of new tools and computational approaches, and studies of how the virome interacts with the human body and other microbes. Together, these efforts have the potential to significantly expand our understanding of how the virome is established, how it changes over time and across the lifespan, how it responds to factors such as aging and the environment, and how it contributes to human physiology. 

KB: The panel discussion at ASM 2026 is centered around the HVP being two years in—how do you think our understanding of the human virome has changed over those two years? 

CL: Within just two years, we have a new appreciation for the breadth of viruses in our bodies and how our immune system regulates them. We’ve already gained an appreciation for how vast the virome is—we have cataloged thousands of unique viral strains in healthy individuals.

Further, our group has helped identify several dozens of regions in the human genome that are important for regulating how the virome is composed across our population. 

YH-K: We are already learning a great deal about the human virome, including strategies for optimal workflows, sequencing and analysis approaches, and critical ethical considerations. 

BM and LB: The bulk of the effort in the HVP over the past two years has been dedicated to advancing efforts to systematically characterize the human virome and build the tools and infrastructure needed to study it at scale. This includes generating data from a wide range of people, improving methods for identifying and analyzing viruses, and beginning to organize these data into shared resources. The program has also established multiple research centers and coordinated efforts across virome characterization, tool and method development, and functional studies.

These efforts are helping to move the field toward a more comprehensive and coordinated understanding of the human virome.  

KB: How do you predict or hope that work from the HVP might contribute to healthcare and our understanding of disease over the next few years? 

CL: One of my favorite motivating examples is the Epstein-Barr virus (EBV), an endemic virus that >90% of us in the US and UK have been infected by. While EBV initially gives you mononucleosis when you are infected (typically as a teenager), the negative health impacts of the virus typically aren’t seen for decades, where we now know that a rare subset of us infected by EBV will develop multiple sclerosis. What this means is that infections that we encounter early in life may not look bad, but one day may cause chronic diseases. Our ability to understand how infections from viruses later influence our health, especially for complex conditions with no single cause, is going to be transformative. 

YH-K: We know from historical data that viral outbreaks have claimed more lives than death due to cancer, heart disease, and traffic accidents combined; therefore, the hope and promise is that data and knowledge generated from the HVP will help save lives and help with pandemic preparedness. Additional areas of promise are the generation of novel diagnostics, therapeutics, development of novel tools for science, and improved understanding of the role of the virome in health and disease. 

BM and LB: By improving our understanding of the human virome and its interactions with the body, the HVP has the potential to provide new insights into human health and development. Over time, this work may help identify viral factors associated with disease, including chronic and autoimmune conditions, while also uncovering viruses that support health and resilience.

It may also contribute to future diagnostic or therapeutic approaches by improving our understanding of how viral communities change with aging, environmental factors, and health status. For instance, ongoing research is developing targeted phage therapy to remove harmful bacteria or to help build healthy microbiomes that keep dangerous bacteria from taking hold.. More broadly, the HVP will create foundational knowledge and resources that can inform future research into disease and health. 

 

Staff members from the Human Virome Program, including Pamela Birriel, Stacy Carrington-Lawrence, Leia Novak, Hye-Sook Kim, Amanda Melillo, Emmanuel Mongodin, Roberto Flores-Munguia, and Shimian Zou contributed to the responses given by Dr. Becky Miller and Dr. Liliana Brown.