Childhood Stress – Herpes Simplex
A study published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) indicates that a stressful early childhood history affects the long-term functioning of the immune system, specifically evidenced by a secretion of higher levels of herpes simplex virus (HSV)-antibodies into saliva.
Herpes simplex virus or cold sores in children are small blisters around the mouth caused by the herpes simplex virus. They are sometimes called fever blisters. The most common cause of cold sores is the virus called herpes simplex virus 1. The herpes simplex virus in a cold sore is contagious. The virus can also be spread to others 24 to 48 hours before the cold sore appears.
A child is more at risk for cold sores if they live with someone infected with the herpes simplex virus. Once a child is infected with the herpes simplex virus, the virus becomes inactive (dormant) for long periods of time. It can then become active at any time and cause cold sores again. The cold sores usually don’t last longer than a few days, or up to 2 weeks.
The link between psychological stress and reactivation of latent herpes simplex virus, and the manifestation of clinical symptoms such the cold sores is well-known. A recent meta-analysis confirmed the presence of a robust connection between psychosocial stress and symptomatic HSV recurrence. Interestingly, psychosocial stress tended to be more strongly associated with oral than genital herpes recurrence.
Recently, stress has been linked to an early onset and delayed resolution of herpetic lesions, reduced viral clearance at the site of infection and draining popliteal lymph nodes (PLNs), and impaired functions of HSV-specific CD8(+) T cells in PLNs. Of note, in mice, these impaired CD8(+) T cell functions are not due to direct effects of stress/corticosterone on the T cells, but the ability of PLN-derived dendritic cells to prime HSV-1-specific CD8(+) T cells is functionally impaired.
In the PNAS article Elizabeth Shirtcliff, Christopher Coe and Seth Pollak studied two different types or groups of adverse childhood experiences. First, a group of postinstitutionalized adolescents who had experienced early caregiving deprivation before adoption into a more normative family context, and second, a sample of adolescents who had experienced substantiated physical abuse and were still residing within their families of origin.
Across 4 school and home days, the authors found that the HSV antibody was higher in both postinstitutionalized and physically-abused adolescents when compared with control participants. These data revealed that a profile of high HSV antibody serves as a sentinel marker of a history of adverse experience during formative development.
The findings are particularly noteworthy because of the clear demonstration that these effects linger even after the resolution of the period of childhood adversity.
The present study is unique in demonstrating these effects with a pediatric population. In the case of the postinstitutionalized adolescents, they had been adopted into more benevolent family conditions by 2.8 years of age on average.
Thus, for many, the period of adversity had been over for nearly a decade before the current assessment. The authors conclude that the susceptibility of the immune system to early caregiving experiences reveals an important aspect of developmental plasticity.
Source: Proc Natl Acad Sci USA 2009, 106:2963
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An Update
Early-life stress is a risk factor in the development of psychiatric disorders. One possibility is that early-life stress may impair adaptive immunity and, therefore, increase vulnerability to initial infection and subsequent reactivation of herpesviruses. Herpesviruses are potential immune-modifying agents that persist as latent infections and can reactivate during periods of stress.
Initially believed to be benign except in cases of immunosuppression, cytomegalovirus (CMV) infection has been found to be associated with a range of negative outcomes, including depression, immunosenescence, neurodegenerative disorders, and reduced lifespan.
In 2019 Bart N. Ford et al. demonstrated that individuals with major depressive disorder who experienced more early-life stress were more likely to test positive for CMV, and this finding was replicated in a confirmation sample despite substantially different inclusion and exclusion criteria.
The study published in JAMA Psychiatry suggests that early CMV infection and subsequent reactivation during stressful periods may be a mechanism through which the consequences of early-life stress affect health.
The study adds vulnerability to CMV (and potentially to other viruses such as herpes simplex virus 1) to the list of consequences of early-life stress. These findings also highlight an avenue of future research that could potentially validate the proposed mechanistic link between herpesviruses and the sequalae of early-life stress and leverage this association to improve clinical outcomes.
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