Association between Cytomegalovirus Antibody Levels and Cognitive Functioning in Non-Elderly Adults

Dickerson, Faith; Stallings, Cassie; Origoni, Andrea; Katsafanas, Emily; Schweinfurth, Lucy; Savage, Christina; Yolken, Robert H.

doi:10.1371/journal.pone.0095510

Cited by 36 publications

(19 citation statements)

References 23 publications

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“…In addition, macaque N10 also presented with detectable cytomegalovirus (CMV) in the brain. Progression to AIDS is often accompanied by infection with opportunistic pathogens, and CMV is among a subset of pathogens able to enter the brain and potentially lead to neuronal dysregulation (75). However, the qualitative and quantitative results of our study suggest that SIV infection, and not CMV, was the driving factor in the development of SIVE.…”

Section: Discussioncontrasting

confidence: 55%

Evolution of Neuroadaptation in the Periphery and Purifying Selection in the Brain Contribute to Compartmentalization of Simian Immunodeficiency Virus (SIV) in the Brains of Rhesus Macaques with SIV-Associated Encephalitis

Rife

Nolan

Lamers³

et al. 2016

J Virol

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The emergence of a distinct subpopulation of human or simian immunodeficiency virus (HIV/SIV) sequences within the brain (compartmentalization) during infection is hypothesized to be linked to AIDS-related central nervous system (CNS) neuropathology. However, the exact evolutionary mechanism responsible for HIV/SIV brain compartmentalization has not been thoroughly investigated. Using extensive viral sampling from several different peripheral tissues and cell types and from three distinct regions within the brain from two well-characterized rhesus macaque models of the neurological complications of HIV infection (neuroAIDS), we have been able to perform in-depth evolutionary analyses that have been unattainable in HIV-infected subjects. The results indicate that, despite multiple introductions of virus into the brain over the course of infection, brain sequence compartmentalization in macaques with SIV-associated CNS neuropathology likely results from late viral entry of virus that has acquired through evolution in the periphery sufficient adaptation for the distinct microenvironment of the CNS. IMPORTANCEHIV-associated neurocognitive disorders remain prevalent among HIV type 1-infected individuals, whereas our understanding of the critical components of disease pathogenesis, such as virus evolution and adaptation, remains limited. Building upon earlier findings of specific viral subpopulations in the brain, we present novel yet fundamental results concerning the evolutionary patterns driving this phenomenon in two well-characterized animal models of neuroAIDS and provide insight into the timing of entry of virus into the brain and selective pressure associated with viral adaptation to this particular microenvironment. Such knowledge is invaluable for therapeutic strategies designed to slow or even prevent neurocognitive impairment associated with AIDS. Human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) remain a persistent complication despite the success of highly active antiretroviral therapy (HAART) in prolonging the progression to AIDS in HIV-1-infected patients (1). Although the post-HAART era has witnessed a decrease in the prevalence of the most severe form of HAND, HIV-associated dementia (HAD), an increase in prevalence has been observed for the milder forms, referred to as asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorder (MND) (2, 3). Moreover, these assessments have been reported to be an underestimation of the true prevalence, based on a study in which approximately 64% of HIV-1-infected patients classified as "noncomplainers," self-reporting no symptoms of cognitive impairment, tested positive for HAND using comprehensive neurocognitive testing criteria (4). Furthermore, with the life expectancy for patients receiving HAART now projected to be greater than 70 years (5, 6), the reported prevalence estimations can only be expected to increase, whereas our understanding of the critical components of disease pathogenesis, such as t...

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Section: Discussioncontrasting

confidence: 55%

Evolution of Neuroadaptation in the Periphery and Purifying Selection in the Brain Contribute to Compartmentalization of Simian Immunodeficiency Virus (SIV) in the Brains of Rhesus Macaques with SIV-Associated Encephalitis

Rife

Nolan

Lamers³

et al. 2016

J Virol

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“…In this cohort, levels of CMV antibody were extremely high and increased further over the 3 months (Ariyanto et al, submitted for publication). This highlights the challenge of assessing the footprint of CMV when all individuals have high antibody levels, even though CMV seropositivity has been associated with cognitive impairment in middle aged and older adults without HIV [90]. CMV potentiates the development of an Immune Risk Phenotype in HIV patients [91].…”

Section: Neurocognitive Diseasementioning

confidence: 99%

HIV patients, healthy aging and transplant recipients can reveal the hidden footprints of CMV

Waters

Brook

Lee

et al. 2018

Clinical Immunology

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Cytomegalovirus (CMV) is a β-herpesvirus. Latent infections are common in all populations. However age-associated increases in levels of CMV-reactive antibody are testament to repeated reactivations and periods of viral replication. CMV has been associated with several diseases of aging, including vasculopathy and neurocognitive impairment. These conditions occur at a younger age in persons with particularly high burdens of CMV - transplant recipients and people living with HIV. Here we define the "clinical footprints" as immunopathologies triggered by CMV that develop over many years. A high burden of CMV also drives accumulation of multifunctional terminally-differentiated αβ T-cells, a novel population of Vδ2 γδ T-cells, and a population of CD56 NK cells lacking a key regulatory molecule. An understanding of these "immunological footprints" of CMV may reveal how they collectively promote the "clinical footprints" of the virus. This is explored here in transplant recipients, HIV patients and healthy aging.

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“…38 Also, childhood exposure to Epstein-Barr virus was associated with an increased risk of psychotic episodes in adolescents. 39 The association between exposure to infectious agents and a decreased level of cognitive functioning is also supported by studies in adults; exposures to HSV type 1, 40 cytomegalovirus, 41 and Toxoplasma gondii 39 were correlated with decreased levels of cognitive functioning, particularly in domains associated with memory.…”

Section: The Impact Of Inflammation On Neurodevelopment During Adolesmentioning

confidence: 82%

Neurodevelopment: The Impact of Nutrition and Inflammation During Adolescence in Low-Resource Settings

Galler

Koethe

Yolken³

2017

Pediatrics

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Approximately 1 out of 5 children worldwide suffers from childhood malnutrition or stunting and associated health conditions, including an increased susceptibility to infections and inflammation. Due to improved early interventions, most children even in low-resource settings now survive early childhood malnutrition, yet exhibit continuing evidence of neurodevelopmental deficits, including poor school achievement and behavioral problems. These conditions are compounded in children who continue to be undernourished throughout the adolescent years. At present, these sequelae of malnutrition and infection are of major concern in the adolescent population, given that young people between the ages of 10 and 24 years represent nearly one-quarter of the world’s population. Therefore, there is an urgent need to focus on the well-being of this age group and, in particular, on behavioral, cognitive, and brain disorders of adolescents who experienced malnutrition, infection, and inflammation prenatally, in early childhood, and during adolescence itself. Because one-third of all women globally become pregnant during their adolescent years, brain and behavioral disorders during this period can have an intergenerational impact, affecting the health and well-being of the next generation. This article summarizes the current state of knowledge and evidence gaps regarding childhood and adolescent malnutrition and inflammation and their impact on adolescent neurodevelopment, the limited evidence regarding nutrition and psychosocial interventions, and the role of resilience and protective factors in this age group. This overview should help to inform the development of new strategies to improve the neurodevelopmental outcomes of high risk adolescent populations.

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Association between Cytomegalovirus Antibody Levels and Cognitive Functioning in Non-Elderly Adults

Cited by 36 publications

References 23 publications

Evolution of Neuroadaptation in the Periphery and Purifying Selection in the Brain Contribute to Compartmentalization of Simian Immunodeficiency Virus (SIV) in the Brains of Rhesus Macaques with SIV-Associated Encephalitis

Evolution of Neuroadaptation in the Periphery and Purifying Selection in the Brain Contribute to Compartmentalization of Simian Immunodeficiency Virus (SIV) in the Brains of Rhesus Macaques with SIV-Associated Encephalitis

HIV patients, healthy aging and transplant recipients can reveal the hidden footprints of CMV

Neurodevelopment: The Impact of Nutrition and Inflammation During Adolescence in Low-Resource Settings

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