Why Viruses Could Be the Cause of Chronic Disease | Dr. Paul Ewald

Summary

Dr. Paul Ewald argues that infections may contribute to more chronic diseases than is generally recognized. He emphasizes that chronic illness is likely to arise from interacting causes—including pathogens, genetic susceptibility, lifestyle, and social and environmental conditions—rather than from any one factor alone. Many of the infectious links discussed are hypotheses or active research questions, not established explanations.

Scientific Concepts and Examples

• Alzheimer’s disease and oral pathogens: Ewald discusses associations between Alzheimer’s disease and bacteria linked to gum disease and periodontitis, including Porphyromonas gingivalis. He proposes that pathogens entering the bloodstream could affect the brain. Amyloid-beta may have antimicrobial activity, so its production—and the resulting plaques—could be part of a response to infection as well as a source of harm. This is presented as a possible explanation, not a settled account of Alzheimer’s.
• Genetics and infection: The APOE ε4 variant is associated with higher Alzheimer’s risk. Ewald suggests that some genetic risk may reflect vulnerability to particular pathogens, including Chlamydia pneumoniae and herpes simplex virus 1. He describes an evolutionary “arms race”: pathogens change quickly, while host resistance and immune defenses also evolve.
• Connections among chronic diseases: The interview discusses periodontal pathogens in relation to Alzheimer’s disease, atherosclerosis, and diabetes. One proposed feedback loop is that infection may interfere with insulin-related glucose uptake, while elevated blood glucose may worsen infection-related problems. These links require further testing.
• Multiple sclerosis and Epstein–Barr virus (EBV): Ewald points to evidence linking EBV with multiple sclerosis (MS), including genetic findings, the high prevalence of substantial EBV infection among people with MS, and the association between infectious mononucleosis and later MS risk. Because EBV is also common among people without MS, infection alone does not explain who develops the disease. The discussion distinguishes a virus that merely triggers an immune response from one that continues to drive disease.
• Persistent viral activity: A virus may remain active without producing many viral particles. Ewald argues that “latent” can be misleading if a virus is still altering host-cell behavior. He also describes evidence suggesting that enteroviruses may continue to contribute to type 1 diabetes by provoking immune damage to insulin-producing pancreatic cells.
• Viruses and cancer: Some viruses can alter cell-cycle controls, reduce programmed cell death, and allow cells to divide beyond normal limits. These changes may create conditions in which additional mutations can lead to cancer. Ewald argues that infection-based and mutation-based explanations should be considered together.
  • HPV is an established cause of cervical cancer; the interview also discusses its link to oropharyngeal cancer.
  • EBV is described as an established cause of some stomach cancers, nasopharyngeal cancer, and a substantial portion of Hodgkin lymphoma. Its possible roles in breast cancer and other diseases remain under investigation.
  • Hepatitis B and C are discussed as causes of liver cancer. A herpesvirus associated with Kaposi sarcoma is another example of an infection–cancer link.
  • In Hodgkin lymphoma, the cancerous Reed–Sternberg cells may be EBV-infected even when most cells in the tumor are not. This illustrates why the presence of a virus in only a small fraction of tumor cells does not, by itself, rule out a causal role.
  • The possible role of cytomegalovirus in glioblastoma remains contested. Ewald cites reports of longer survival with antiviral treatment, while noting that the evidence is ambiguous and that the treatment might also affect ordinary cell replication.
• Transmission and persistence: Ewald suggests that pathogens spread through sex or intimate kissing may face evolutionary pressure to persist because transmission opportunities can be separated by long periods. Persistent infections may therefore be relevant to chronic disease, though this does not establish that any particular infection causes a given illness.
• Cancer and mitochondria: Asked whether viruses might cause cancer by damaging mitochondria, Ewald says he does not know of an established answer. He presents it as a research question, including the possibility of indirect effects.
• Acute versus chronic infection: The interview describes acute infections as those usually controlled by the immune system over weeks, while infections that evade control may persist for months or years. This is a broad conceptual distinction, not a strict diagnostic cutoff.
• Prevention and treatment: The discussion notes existing vaccines against HPV, hepatitis B, and shingles, while saying that vaccines for EBV and C. pneumoniae were not available at the time described. It recommends evaluating vaccines and treatments disease by disease. Ewald also discusses oral hygiene, sleep, diet, exercise, stress reduction, and limiting pathogen exposure as practices that may support health. These should not be read as proven ways to prevent the diseases discussed or as a substitute for medical care.

Research Approach and Caveats

• Combine epidemiological, genetic, immunological, molecular, clinical, and cultural evidence rather than relying on one kind of study.
• Look for mechanisms linking a pathogen to tissue damage, and test those mechanisms in appropriate models, including animal studies where relevant.
• Interpret associations carefully, especially when a pathogen is common in people both with and without a disease.
• Consider that a virus may be present in only a small number of tumor cells, or may have initiated changes that persist after the virus is no longer detectable.
• Use meta-analyses to assess findings across studies, while recognizing that inconsistent methods and results can complicate interpretation.
• Test whether an infection is only a trigger or continues to contribute to disease, including through intervention studies where feasible.
• Treat the interview’s proposed infectious links as hypotheses of varying strength. Some infection–cancer relationships are established, while others remain debated or preliminary.

Researchers and Sources Featured

• Dr. Paul Ewald — Evolutionary biologist interviewed and author of Plague Time: The New Germ Theory of Disease.
• Holly Swain — Ewald’s collaborator, described as having worked on glioblastoma.
• Peyton Rous — Researcher credited in the interview with identifying a viral cause of cancer in chickens.
• Aasta SS — Host of the interview.
• Stanford study — Unnamed study discussed in connection with EBV and multiple sclerosis.
• Karolinska Institute — Site of antiviral-treatment research on glioblastoma discussed in the interview.
• NIH — Mentioned in the discussion of funding for research on EBV and breast cancer.
• Studies and reviews — The interview refers generally to Alzheimer’s research, mouse studies, meta-analyses, and medical review papers; no specific papers or authors are named.