About

Walter J. Atwood is the Viatris Professor of Biology and Medicine at Brown University, where he also serves as Chair of Molecular Biology, Cell Biology and Biochemistry, and as a Professor of Neurology. His academic background includes a B.S. in Microbiology and a Ph.D. in Neurovirology from the University of Massachusetts, Amherst. His research focuses on neurovirology, virology, cell biology, genomics, and proteomics, with particular emphasis on JC Polyomavirus (JCPyV), BK polyomavirus, and related viruses. Dr. Atwood's work involves understanding the mechanisms of virus infection, entry, and spread, as well as the development of potential therapeutics for virus-associated diseases. His contributions include elucidating the restrictive nature of the blood-brain barrier to JC Polyomavirus neuroinvasion, investigating extracellular vesicle biogenesis in JC virus infection, and exploring receptor-dependent and -independent mechanisms of virus infection. Throughout his career, he has published extensively on virus-host interactions, viral entry pathways, and potential antiviral strategies, making significant contributions to the field of neurovirology and molecular virology.

Research topics

• Pathology
• Medicine
• Virology
• Immunology
• Biology
• Political Science
• Neuroscience
• Cell biology

Selected publications

• Living on the Edge: The Goldilocks Zone of Polyomavirus Replication and Persistence

  Viruses · 2026-05-19

  articleOpen accessSenior author

  BK and JC Polyomaviruses (BKPyV and JCPyV) are ubiquitous human pathogens capable of establishing lifelong, asymptomatic persistence in the majority of the global population. While decades of research have focused on their lytic replication cycles and the development of severe diseases, such as polyomavirus-associated nephropathy (PVAN) caused by BKPyV and progressive multifocal leukoencephalopathy (PML) caused by JCPyV, their primary evolutionary strategy is one of persistence rather than pathogenesis. This review shifts the perspective from a replication-centric framework towards an evolutionary persistence model, detailing the multi-layered host and viral determinants that maintain the homeostatic balance. At the cellular level, viral genomes are restricted by chromatinization into minichromosomes and host S-phase licensing. These constraints are reinforced by innate immune sensing and adaptive T-cell and antibody responses that curtail systemic dissemination while permitting periodic, low-level urinary shedding, which is essential for horizontal transmission. In addition to these host barriers, the viruses utilize intrinsic regulatory mechanisms to prevent excessive replication and immune detection, including the stable archetype non-coding control region (NCCR), viral microRNAs that downregulate early gene expression, and the small t antigen (STAg). Finally, we address unresolved questions regarding the full spectrum of cellular reservoirs, the molecular triggers of reactivation, and the ecological factors shaping their transmission routes. Understanding these maintenance mechanisms is crucial for refining clinical interventions and managing the rare, devastating transitions from silent persistence to lytic disease.

  PublisherDOI

• JC polyomavirus neuroinvasion across the blood-brain barrier: Current understanding and emerging perspectives

  Tumour Virus Research · 2025-11-20 · 4 citations

  articleOpen accessSenior author

  JC Polyomavirus (JCPyV) is the causative agent of progressive multifocal leukoencephalopathy (PML), an often-fatal demyelinating disease. Unfortunately, a diagnosis of PML occurs only after patients have suffered irreversible neuropathologies. One requirement for the development of PML is for JCPyV to enter the brain, but the mechanisms responsible for neuroinvasion have not been well established. The blood-brain barrier (BBB) is a potential site for JCPyV neuroinvasion. JCPyV DNA is found in the vascular endothelium in postmortem brain tissue from PML patients, and demyelinating lesions commonly emerge around vascularized sites. This review explores three potential pathways that may underlie JCPyV traversal across the BBB: diapedesis ("Trojan Horse") via JCPyV-associated B cells, paracellular passage, and transcytosis. Elucidating the route and mechanism of JCPyV neuroinvasion will deepen our understanding of how the virus enters the brain before the manifestation of PML neuropathologies. Additionally, we discuss current limitations of in vitro BBB modeling and propose future approaches to more accurately capture the physiological dynamics underlying JCPyV neuroinvasion.

  PublisherDOI

• Therapeutic potential of flavonols in the treatment of JCPyV

  Microbiology Spectrum · 2025-08-21 · 1 citations

  articleOpen accessSenior author

  JC polyomavirus (JCPyV) is a double-stranded DNA virus that causes progressive multifocal leukoencephalopathy (PML), a demyelinating disease with a high rate of morbidity and mortality. There are limited treatment options for patients diagnosed with PML, and most involve reconstitution of immunological functions. In this paper, we show that flavonols, specifically quercetin, myricetin, and fisetin, significantly reduce JCPyV infection in human glial cells. We further show that quercetin and fisetin can suppress viral spread in an already established infection, suggesting therapeutic viability of these drugs as antivirals. Additional research is required to determine the mechanism of action of flavonols in inhibiting JCPyV infection and to investigate whether these compounds have the potential to cross the blood-brain barrier in significant amounts to inhibit the virus in the brain parenchyma.IMPORTANCEThe human polyomavirus, JC polyomavirus (JCPyV), causes significant morbidity and mortality in immunosuppressed or immunomodulated patients. There are no approved antivirals to treat JCPyV-induced disease. Flavonols are naturally occurring polyphenolic compounds that are known to antagonize pathways involved in JCPyV infection. Several flavonols were found to inhibit initial JCPyV infection and viral spread in a glial cell line and in normal human glial cells. These represent a promising new treatment paradigm for patients at risk of suffering from JCPyV-induced disease.

  PublisherDOI

• Neurovascular pericytes are susceptible to infection by JC polyomavirus

  Journal of Virology · 2025-08-14 · 4 citations

  articleOpen access

  Progressive multifocal leukoencephalopathy (PML), an often-fatal neurodegenerative disease, is caused by the neuroinvasive polyomavirus JCPyV. Peripheral organs, including the kidney, are the site of lifelong persistent infections that are asymptomatic. In a subset of immunosuppressed or immunomodulated patients, the virus invades the central nervous system infecting oligodendrocytes, which leads to the multifocal white matter disease known as PML. The mechanisms that lead to neuroinvasion by JCPyV have not been well described. The brain is protected from viruses and other pathogens by physiological barriers, including the blood-cerebrospinal fluid barrier and the blood-brain barrier. To better understand the mechanism by which the virus breaches these barriers, we focused our attention on studying virus interactions with pericytes, which are an essential component of the blood-brain barrier. We found that the virus binds to pericytes in a receptor-dependent manner and that pericytes are susceptible to JCPyV infection. Previous work from our group demonstrated that JCPyV was capable of penetrating an intact endothelial cell barrier. Once across the endothelium, JCPyV would come in direct contact with pericytes, and we hypothesize pericyte infection would amplify and facilitate robust penetration into the brain parenchyma. This is the first demonstration that pericytes, a principal component of the blood-brain barrier, are susceptible to the neuroinvasive human polyomavirus JCPyV.IMPORTANCEJCPyV infects at least half the adult population worldwide. An asymptomatic, persistent infection is typically established in the kidney and possibly other peripheral organs. In immunosuppressed individuals, the virus can reactivate and cause progressive multifocal leukoencephalopathy, a deadly disease of the central nervous system (CNS). The pathogenic route the virus takes from the periphery to the CNS is unknown. Here, we demonstrate for the first time that JCPyV can infect human cerebrovascular pericytes, a cell type that contributes to the blood-brain barrier. This observation suggests that the virus could use the pericytes as a means to penetrate the blood-brain barrier to reach its pathogenic targets in the brain parenchyma.

  PublisherDOI

• The microvascular endothelium of the blood-brain barrier is highly restrictive to JC Polyomavirus neuroinvasion

  Microbiology Spectrum · 2025-03-25 · 3 citations

  articleOpen accessSenior author

  JC Polyomavirus is the causative agent of progressive multifocal leukoencephalopathy (PML), an often-fatal demyelinating disease. Unfortunately, a diagnosis of PML occurs only after patients have suffered irreversible neuropathologies. The first step in the initiation of PML is viral entry to the brain, but the route and mechanisms responsible for neuroinvasion have not been well established. To gain a better understanding of this, we asked whether purified virus or virus associated with extracellular vesicles (EVs) could penetrate two different cell culture models of the blood-brain barrier. In one model, we used the hCMEC/D3 brain endothelial cell line, and in the other, we used pluripotent stem cells induced to a brain endothelial cell phenotype (iPSC-EC). We found that neither cell type was permissive to viral infection, but the virus bound and was internalized by both in a sialic acid-dependent manner. Despite virus internalization into these cells, very few virions or virus-associated extracellular vesicles (virus-EVs) penetrated the barriers. The small amount of virus or virus-EVs that did pass through either barrier was sufficient to establish infection in human glial cells. Our findings demonstrate that limited amounts of infectious virions and virus-associated EVs can traverse the brain microvascular endothelium and establish infection.IMPORTANCEThe human polyomavirus, JC Polyomavirus (JCPyV), causes a rapidly progressing demyelinating disease in immunocompromised or immunomodulated patients. Demyelinating lesions are often seen surrounding blood vessels in the brain. In this paper, we used two models to recapitulate a minimal blood-brain barrier and found that both were highly restrictive of virus penetration. A small amount of virus succeeded in crossing both barriers and was sufficient to establish infection of human glia. These data have direct implications for mechanisms used by JCPyV to invade the CNS and cause neurological disease.

  PublisherDOI

• Highly restrictive and directional penetration of the blood cerebral spinal fluid barrier by JCPyV

  PLoS Pathogens · 2024-07-22 · 5 citations

  articleOpen accessSenior authorCorresponding

  The human polyomavirus JCPyV is an opportunistic pathogen that infects greater than 60% of the world's population. The virus establishes a persistent and asymptomatic infection in the urogenital system but can cause a fatal demyelinating disease in immunosuppressed or immunomodulated patients following invasion of the CNS. The mechanisms responsible for JCPyV invasion into CNS tissues are not known but direct invasion from the blood to the cerebral spinal fluid via the choroid plexus has been hypothesized. To study the potential of the choroid plexus as a site of neuroinvasion, we used an adult human choroid plexus epithelial cell line to model the blood-cerebrospinal fluid (B-CSF) barrier in a transwell system. We found that these cells formed a highly restrictive barrier to virus penetration either as free virus or as virus associated with extracellular vesicles (EVJC+). The restriction was not absolute and small amounts of virus or EVJC+ penetrated and were able to establish foci of infection in primary astrocytes. Disruption of the barrier with capsaicin did not increase virus or EVJC+ penetration leading us to hypothesize that virus and EVJC+ were highly cell-associated and crossed the barrier by an active process. An inhibitor of macropinocytosis increased virus penetration from the basolateral (blood side) to the apical side (CSF side). In contrast, inhibitors of clathrin and raft dependent transcytosis reduced virus transport from the basolateral to the apical side of the barrier. None of the drugs inhibited apical to basolateral transport suggesting directionality. Pretreatment with cyclosporin A, an inhibitor of P-gp, MRP2 and BCRP multidrug resistance transporters, restored viral penetration in cells treated with raft and clathrin dependent transcytosis inhibitors. Because choroid plexus epithelial cells are known to be susceptible to JCPyV infection both in vitro and in vivo we also examined the release of infectious virus from the barrier. We found that virus was preferentially released from the cells into the apical (CSF) chamber. These data show clearly that there are two mechanisms of penetration, direct transcytosis which is capable of seeding the CSF with small amounts of virus, and infection followed by directional release of infectious virions into the CSF compartment.

  PublisherOA PDFDOI

• Correction for Querbes et al., “A JC Virus-Induced Signal Is Required for Infection of Glial Cells by a Clathrin- and eps15-Dependent Pathway”

  Journal of Virology · 2024-03-26

  articleOpen accessSenior author

  Volume 78, no. 1, p. 250–256, 2004, https://doi.org/10.1128/jvi.78.1.250-256.2004. The authors wish to correct the scientific record relating to Fig. 1 and 2 of the above-referenced paper, where four panels of control images within Fig. 1A and 2A were not described sufficiently in the figure legends and appear to be duplicates. This omission, which we have now corrected, had no bearing on the conclusions reached in the paper.

  PublisherOA PDFDOI

• JCPyV infection of primary choroid plexus epithelial cells reduces expression of critical junctional proteins and increases expression of barrier disrupting inflammatory cytokines

  Microbiology Spectrum · 2024-06-14 · 6 citations

  articleOpen accessSenior author

  ABSTRACT The human polyomavirus, JCPyV, establishes a lifelong persistent infection in the peripheral organs of a majority of the human population worldwide. Patients who are immunocompromised due to underlying infections, cancer, or to immunomodulatory treatments for autoimmune disease are at risk for developing progressive multifocal leukoencephalopathy (PML) when the virus invades the CNS and infects macroglial cells in the brain parenchyma. It is not yet known how the virus enters the CNS to cause disease. The blood-choroid plexus barrier is a potential site of virus invasion as the cells that make up this barrier are known to be infected with virus both in vivo and in vitro . To understand the effects of virus infection on these cells we challenged primary human choroid plexus epithelial cells with JCPyV and profiled changes in host gene expression. We found that viral infection induced the expression of proinflammatory chemokines and downregulated junctional proteins essential for maintaining blood-CSF and blood-brain barrier function. These data contribute to our understanding of how JCPyV infection of the choroid plexus can modulate the host cell response to neuroinvasive pathogens. IMPORTANCE The human polyomavirus, JCPyV, causes a rapidly progressing demyelinating disease in the CNS of patients whose immune systems are compromised. JCPyV infection has been demonstrated in the choroid plexus both in vivo and in vitro and this highly vascularized organ may be important in viral invasion of brain parenchyma. Our data show that infection of primary choroid plexus epithelial cells results in increased expression of pro-inflammatory chemokines and downregulation of critical junctional proteins that maintain the blood-CSF barrier. These data have direct implications for mechanisms used by JCPyV to invade the CNS and cause neurological disease.

  PublisherDOI

• Virology under the Microscope—a Call for Rational Discourse

  mSphere · 2023 · 9 citations

  • Political Science
  • Virology
  • Medicine

  Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns - conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we - a broad group of working virologists - seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology.

  PublisherDOI

• Virology under the Microscope—a Call for Rational Discourse

  mBio · 2023-01-26 · 4 citations

  articleOpen access

  Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns - conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we - a broad group of working virologists - seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology.

  PublisherDOI

Recent grants

• NIH Grant R29CA071878

  NIH · $445k · 2002

• CORE A: Administrative Core

  NIH · $24.7M · 2009–2020

• NIH Grant P20RR015578

  NIH · $9.0M · 2012

• NIH Grant R01CA071878

  NIH · $2.6M · 2013

• Center for Cancer Signaling Networks

  NIH · $4.3M · 2011–2017

Frequent coauthors

• Bethany A. O’Hara

  Providence College

  138 shared

• Gretchen V. Gee

  University of Massachusetts Chan Medical School

  104 shared

• Sheila A. Haley

  Providence College

  64 shared

• Melissa S. Maginnis

  University of Maine

  49 shared

• Christian D. S. Nelson

  SUNY Cortland

  47 shared

• Aisling S. Dugan

  Tufts University

  42 shared

• Benedetta Assetta

  Allen Institute for Brain Science

  38 shared

• Kate Manley

  Novartis (Switzerland)

  37 shared

Education

• B.S., Microbiology

  University of Massachusetts, Amherst

  1986

• Ph.D., Neurovirology

  University of Massachusetts, Amherst

  1991