HERVs: Expression Control Mechanisms and Interactions in Diseases and Human Immunodeficiency Virus Infection.

Human endogenous retroviruses (HERVs) are the result of retroviral infections acquired millions of years ago; nowadays, they compose around 8% of human DNA. Multiple mechanisms have been employed for endogenous retroviral deactivation, rendering replication and retrotransposition defective, while some of them have been co-opted to serve host evolutionary advantages. A pleiad of mechanisms retains the delicate balance of HERV expression in modern humans. Thus, epigenetic modifications, such as DNA and histone methylation, acetylation, deamination, chromatin remodeling, and even post-transcriptional control are recruited. In this review, we aim to summarize the main HERV silencing pathways, revisit paradigms of human disease with a HERV component, and emphasize the human immunodeficiency virus (HIV) and HERV interactions during HIV infection.

The interaction of human immunodeficiency virus-1 and human endogenous retroviruses in patients (primary cell cultures) and cell line models.

IMPORTANCE: In this work, we demonstrated that human immunodeficiency virus (HIV) infection leads to the modification of the human endogenous retrovirus (HERV) expression. Differential expression of multiple HERVs was found in peripheral blood mononuclear cells derived from HIV-infected patients compared to healthy donors and HIV-infected T cell cultures compared to non-infected. The effect of HIV presence on HERV expression appears to be more restricted in cells of monocytic origin, as only deregulation of HERV-W and HERV-K (HML-6) was found in these cell cultures after their infection with HIV. Multiple factors contribute to this aberrant HERV expression, and its levels appear to be modified in a time-dependent manner. Further studies and the development of optimized in vitro protocols are warranted to elucidate the interactions between HIV and HERVs in detail.

Multistimulation group therapy in Alzheimer's disease promotes changes in brain functioning.

Background. The growing social emergency represented by Alzheimer's disease (AD) and the lack of medical treatments able to modify the disease course have kindled the interest in nonpharmacological therapies. Objective. We introduced a novel nonpharmacological approach for people with AD (PWA) named Multidimensional Stimulation group Therapy (MST) to improve PWA condition in different disease domains: cognition, behavior, and motor functioning. Methods. Enrolling 60 PWA in a mild to moderate stage of the disease, we evaluated the efficacy of MST with a randomized-controlled study. Neuropsychological and neurobehavioral measures and functional magnetic resonance imaging (fMRI) data were considered as outcome measures. Results. The following significant intervention-related changes were observed: reduction in Neuropsychiatric Inventory scale score, improvement in language and memory subscales of Alzheimer's Disease Assessment Scale-Cognitive subscale, and increased fMRI activations in temporal brain areas, right insular cortex, and thalamus. Conclusions. Cognitive-behavioral and fMRI results support the notion that MST has significant effects in improving PWA cognitive-behavioral status by restoring neural functioning.

Functional brain changes in early Parkinson's disease during motor response and motor inhibition.

Motor impairment represents the main clinical feature of Parkinson's disease (PD). Cognitive deficits are also frequently observed in patients with PD, with a prominent involvement of executive functions and visuo-spatial abilities. We used event-related functional MRI (fMRI) and a paradigm based on visual attention and motor inhibition (Go/NoGO-task) to investigate brain activations in 13 patients with early PD in comparison with 11 healthy controls. The two groups did not report behavioural differences in task performance. During motor inhibition (NoGO-effect), PD patients compared to controls showed an increased activation in the prefrontal cortex and in the basal ganglia. They also showed a reduced and less coherent hemodynamic response in the occipital cortex. These results indicate that specific cortico-subcortical functional changes, involving not only the fronto-striatal network but also the temporal-occipital cortex, are already present in patients with early PD and no clinical evidence of cognitive impairment. We discuss our findings in terms of compensatory mechanisms (fronto-striatal changes) and preclinical signs of visuo-perceptual deficits and visual hallucinations.

Efficacy of recreational and occupational activities associated to psychologic support in mild to moderate Alzheimer disease: a multicenter controlled study.

We evaluated the efficacy of a stimulation program mainly based on recreational and occupational activities, associated with a brief cycle of support psychotherapy for patients and caregivers, in mild to moderate Alzheimer Disease (AD) associated or not with cerebrovascular lesions. Sixty-seven patients and 31 controls from 2 Italian towns entered the study. The control group was comprised of AD subjects who voluntarily declined to participate in the program for practical reasons. Patients were divided in groups of 4 subjects: treatment was delivered for 6 weeks. Multidimensional efficacy assessment of functional, behavioral, and neuropsychologic aspects was performed. When comparing baseline with posttraining condition, patients displayed a substantial reduction in disruptive behavior, and a tendency to a general reduction of behavioral symptoms compared with controls (Revised Memory and Behavior Problems Checklist--RMBPC--symptoms frequency-total P=0.07; frequency of disruptive behavior P=0.008). This reduction was mirrored by a significant reduction of caregiver reaction to behavioral disturbances (RMBPC caregiver reaction-total P=0.035; reaction to disruptive behavior, P=0.011). At 3 months follow-up, the reduction of caregiver reaction to behavioral symptoms results was confirmed (RMBPC caregiver reaction-total P=0.014, caregiver reaction to disruptive behavior P=0.028). No other significant difference was detected. These results partially confirm findings of previous studies, showing that AD patients treated with similar techniques demonstrated an improvement in behavioral disturbances.

Specific impairments of selective attention in mild Alzheimer's disease.

The aim of the present study was to evaluate selective visual attention in subjects affected by Alzheimer's Disease (AD), by means of a computerized spatial exploration test that adopts a Touch Screen (TS) interface, which has already proved able to characterize alternative strategies in performing search tasks. We assessed a group of 16 patients affected by mild to moderate AD, comparing them with 16 control subjects matched for age and education. In the experimental tasks the performance of the AD patients was worse than that of the normal elderly, both quantitatively (slower speeds) and qualitatively (poorer planning and higher number of omissions and perseverations). In the visual attention tasks there appeared to be no close connection between AD patients' performance and increased Reaction Times (RT); this evidenced a specific role of non-elementary cognitive structures enclosed in a higher attentional domain, rather than a general decrease in the speed of basic cognitive processes. Our results are in line with specific AD literature: while psychomotor speed and lower attention levels (sensorimotor) are preferentially impaired in subcortical forms of dementia, the higher levels of selective and divided attention could be the first to deteriorate and appear more markedly disrupted in the Alzheimer type of dementia.