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How Viruses Vex Vitality: Viral Infections Have Lasting Effects on Immunity and Worsen Aging

How Viruses Vex Vitality: Viral Infections Have Lasting Effects on Immunity and Worsen Aging

Throughout our lifetimes, we are exposed to dozens of different viruses that our immune system will try to contain and defeat. The response that is triggered by these viruses may have long-lasting effects that carry consequences for our overall health.

Also, there is evidence that when an immune response, such as inflammation, becomes chronic, it can lead to the development of chronic diseases and can add to the aging process. New research from the Buck Institute and Stanford University suggests that chronic viral infections have a profound and lasting impact on the human immune system in ways that are like those seen during aging.

Dormant Viruses Can Stay With You For Many Years

In most cases, we clear viruses from our systems with specifically produced immune measures that protect us from future infections. In other cases, we can stop new viral infections but cannot clear them, so the virus remains dormant within our body. As a result, we may carry a library of dormant viruses that will stay with us for the rest of our lives.

"Each of us has our own virome; it's the collection of the viral infections you have during your lifespan," said senior author Dr. David Furman. "You probably have been infected by 12 or 15, or even more viruses that you never knew you had. Fortunately, technology now exists that allows us to profile these infections in the human population; it is helping us move these types of inquiries forward."

Examples of dormant viruses include cytomegalovirus (CMV), an otherwise harmless virus that only becomes an issue in pregnant women or people with weakened immune systems. Herpes viruses can also become dormant after the initial infection, leading to ongoing cycles of flare-ups as harmless as cold sores or as serious as genital infections. Another example is chickenpox, a relatively mild childhood disease that can cause painful blistering known as “shingles” many years after the first infection.

Inflammation and Aging Are Intimately Linked

Aging and age-related diseases share many pathways that have a common denominator — inflammation. Most immune responses start with inflammation. Viral infections, or even just regular immune activity, may cause a state of low-grade chronic inflammation that can speed up changes that are related to aging. This chronic state of inflammation can lead to the development of diseases and accelerated aging — commonly referred to by researchers as “inflammaging” (1).

A new study published in the journal Proceedings of the National Academy of Sciences suggests that chronic viral infections leave a lasting impact on the immune system, similar to the changes seen as part of the aging process (2). The study examined the long-term effects of two viruses, Hepatitis C (HCV), and the human immunodeficiency virus (HIV), on the immune systems of a cohort of aging individuals.  

 chronic viral infections leave a lasting impact on the immune system

Chronic Viral Infections Speed Up Aging

The study followed over 150 people infected with either HIV or HCV. The Buck Institute and Stanford researchers chose HIV because of the effect it has on the immune system. After being infected with HIV, the virus will suppress the host’s immune system until it is no longer effective at fighting infections. Therapies for HIV can stop the virus from replicating and prevent some of the damage caused by the virus. In the same way, we can treat HCV with medication that makes it possible to clear the virus from the patient after a few weeks of treatment.

Dr. Furman said the following of the study, "Whether chronic viral infection contributes to age-associated immune dysfunction is still an open question, but studies of this type provide a way to start getting answers. At this point it's clear that both aging and chronic viral infections leave profound and indelible marks on immunity."

The study used artificial intelligence to compare data between infected and uninfected patients. Results show that the immune systems of the HIV participants had been permanently compromised by damaging a special line of immune cells called memory T cells, even though these participants had been receiving anti-viral treatment for over 10 years. The virus had also disrupted immune processes by reducing sensitivity to cytokines, a major signaling path in the immune system.

The researchers found similar results in the HCV participants, even over a year after the HCV virus had been cleared from their systems. These changes are similar to the dysregulation seen in aging. The results show that clearing these viruses to a level where they are no longer detectable does not improve immune function after the disruption caused by the virus has already taken place. These viruses had damaged their host’s immunity permanently through a chronic inflammatory response to infection.

Further tests showed it was possible to restore some of the sensitivity and function compromised by the viral infections, but the path to effective therapy is still unclear. The dysfunction caused by the inflammatory response persists even after several years of treatment. 

Does COVID-19 Accelerate Aging?

Although these findings show that chronic viral infections leave permanent effects on immunity similar to what is seen in the aging process, do short-term viral infections like COVID-19 also have an effect on immune function and aging?

"Has the immune system of those infected with the coronavirus taken a big hit? That's a theory, but we don't know what will happen," says Furman, who is collaborating with Stanford University and the University of California, San Francisco on projects involving COVID-19 and immunity.


  1. Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 2018;14(10):576-590. doi:10.1038/s41574-018-0059-4
  2.     Lopez Angel CJ, Pham EA, Du H, et al. Signatures of immune dysfunction in HIV and HCV infection share features with chronic inflammation in aging and persist after viral reduction or elimination. Proc Natl Acad Sci U S A. 2021;118(14):e2022928118. doi:10.1073/pnas.2022928118

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