HERV-W upregulation expression in bipolar disorder and schizophrenia: unraveling potential links to systemic immune/inflammation status.

BACKGROUND: Bipolar disorder (BD) and schizophrenia (SZ) are the two main mental disorders with unknown etiology that significantly impact individuals' quality of life. The potential pro-inflammatory role in their pathogenesis is postulated and Human Endogenous Retrovirus W (HERV-W) is an emerging candidate to modulate this pathogenic finding. HERVs, ancient retroviruses in the human genome, may play roles in inflammation and disease pathogenesis. Despite HERVs' involvement in autoimmune diseases, their influence on mental disorders remains underexplored. Therefore, the aim of this study was to assess the level of HERV-W-env expression and the systemic inflammatory profile through the concentration of IL-2, IL-4, IL-6, IL-10, TNF-α and INF-γ cytokines in BD and SZ patients. RESULTS: All participants showed HERV-W-env expression, but its expression was higher in mental disorder patients (p < 0.01) than in control. When separated, SZ individuals exhibited higher HERV-W expression than the control group (p < 0.01). Higher serum levels of TNF-α and IL-10 were found in BD (p = 0.0001 and p = 0.001, respectively) and SZ (p = 0.01) and p = 0.01, respectively) than in the control group, while SZ showed decreased levels IFN-γ and IL-2 as compared to controls (p = 0.05) and BD patients (p = 0.05), respectively. Higher TNF-α/IL-4 and TNF-α/IL-10 ratios, and lower IFN-γ/IL-10 were observed in BD and SZ patients than controls. Significant negative correlation between HERV-W-env expression and IL-10 (r=-0.47 p < 0.05), as well as positive correlations between HERV-W-env expression and TNF-α/IL-10 or IFN-γ/IL-10 ratios (r = 0.48 p < 0.05 and r = 0.46 p < 0.05, respectively) were found in BD patients. CONCLUSION: These findings suggest not only a potential link between HERV-W-env expression both in BD and SZ, but also a possible involvement of systemic inflammatory status in BD patients.

HERV-W Envelope Triggers Abnormal Dopaminergic Neuron Process through DRD2/PP2A/AKT1/GSK3 for Schizophrenia Risk.

An increasing number of studies have begun considering human endogenous retroviruses (HERVs) as potential pathogenic phenomena. Our previous research suggests that HERV-W Envelope (HERV-W ENV), a HERV-W family envelope protein, is elevated in schizophrenia patients and contributes to the pathophysiology of schizophrenia. The dopamine (DA) hypothesis is the cornerstone in research and clinical practice related to schizophrenia. Here, we found that the concentration of DA and the expression of DA receptor D2 (DRD2) were significantly higher in schizophrenia patients than in healthy individuals. Intriguingly, there was a positive correlation between HERV-W ENV and DA concentration. Depth analyses showed that there was a marked consistency between HERV-W ENV and DRD2 in schizophrenia. Studies in vitro indicated that HERV-W ENV could increase the DA concentration by regulating DA metabolism and induce the expression of DRD2. Co-IP assays and laser confocal scanning microscopy indicated cellular colocalization and a direct interaction between DRD2 and HERV-W ENV. Additionally, HERV-W ENV caused structural and functional abnormalities of DA neurons. Further studies showed that HERV-W ENV could trigger the PP2A/AKT1/GSK3 pathway via DRD2. A whole-cell patch-clamp analysis suggested that HERV-W ENV enhanced sodium influx through DRD2. In conclusion, we uncovered a relationship between HERV-W ENV and the dopaminergic system in the DA neurons. Considering that GNbAC1, a selective monoclonal antibody to the MSRV-specific epitope, has been promised as a therapy for treating type 1 diabetes and multiple sclerosis (MS) in clinical trials, understanding the precise function of HERV-W ENV in the dopaminergic system may provide new insights into the treatment of schizophrenia.

Hepatitis C-associated late-onset schizophrenia: a nationwide, population-based cohort study.

BACKGROUND: Whether infection with the hepatitis C virus (HCV) causes schizophrenia - and whether the associated risk reverses after anti-HCV therapy - is unknown; we aimed to investigate these topics. METHODS: We conducted a nationwide, population-based cohort study using the Taiwan National Health Insurance Research Database (TNHIRD). A diagnosis of schizophrenia was based on criteria from the International Classification of Diseases, 9th revision (295.xx). RESULTS: From 2003 to 2012, from a total population of 19 298 735, we enrolled 3 propensity-score-matched cohorts (1:2:2): HCV-treated (8931 HCV-infected patients who had received interferon-based therapy for ≥ 6 months); HCV-untreated (17 862); and HCV-uninfected (17 862) from the TNHIRD. Of the total sample (44 655), 82.81% (36 980) were 40 years of age or older. Of the 3 cohorts, the HCV-untreated group had the highest 9-year cumulative incidence of schizophrenia (0.870%, 95% confidence interval [CI] 0.556%-1.311%; p < 0.001); the HCV-treated (0.251%, 95% CI 0.091%-0.599%) and HCV-uninfected (0.118%, 95% CI 0.062%-0.213%) cohorts showed similar cumulative incidence of schizophrenia (p = 0.33). Multivariate Cox analyses showed that HCV positivity (hazard ratio [HR] 3.469, 95% CI 2.168-5.551) was independently associated with the development of schizophrenia. The HCV-untreated cohort also had the highest cumulative incidence of overall mortality (20.799%, 95% CI 18.739%-22.936%; p < 0.001); the HCV-treated (12.518%, 95% CI 8.707%-17.052%) and HCV uninfected (6.707%, 95% CI 5.533%-8.026%) cohorts showed similar cumulative incidence of mortality (p = 0.12). LIMITATIONS: We were unable to determine the precise mechanism of the increased risk of schizophrenia in patients with HCV infection. CONCLUSION: In a population-based cohort (most aged ≥ 40 years), HCV positivity was a potential risk factor for the development of schizophrenia; the HCV-associated risk of schizophrenia might be reversed by interferon-based antiviral therapy.

COVID-19 Infection-Related Weight Loss Decreases Eating/Swallowing Function in Schizophrenic Patients.

BACKGROUND: In older people with psychoneurological diseases, COVID-19 infection may be associated with a risk of developing or exacerbating dysphagia. The aim of the present study was to examine the relationship between eating/swallowing function and COVID-19 infection. METHODS: Subjects were 44 inpatients with confirmed COVID-19 infection being treated for schizophrenia in a psychiatric ward. Eating function was assessed using the Food Intake Level Scale (FILS) before and after infection. We also evaluated age, comorbidities, COVID-19 hospital stay, obesity index, weight loss rate, and chlorpromazine equivalent. RESULTS: Subjects had a mean age of 68.86 years. Pre-infection, 20 subjects had a FILS score of 7-9 (presence of eating/swallowing disorder) and 24 subjects had a score of 10 (normal). Eating function after infection resolution showed decreasing FILS score compared to that before infection in 14 subjects (74.14 years). Six subjects (79.3 years) transitioned from oral feeding to parenteral feeding. A ≥ 10% weight loss during infection treatment was significantly associated with decreased eating function and a transition to parenteral feeding. Chlorpromazine equivalents, comorbidities, and number of days of hospitalization showed no associations with decreased eating function. CONCLUSIONS: Preventing malnutrition during treatment for COVID-19 infection is important for improving post-infection life prognosis and maintaining quality of life (QOL).

A commentary revisiting the viral hypothesis of schizophrenia: Onset of a schizophreniform disorder subsequent to SARS CoV-2 infection.

The viral hypothesis for schizophrenia has persisted for decades, initially supported by observed increases in psychoses subsequent to the influenza pandemic of the early twentieth century, and then later by evidence of elevated viral antibody titres particularly in schizophrenia patient populations. Several research studies have also focused on maternal infections during the second trimester of pregnancy and their long-term effects on fetal brain development, ultimately leading to schizophrenia. No specific virus has been implicated although a handful have received increasing attention. The current pandemic spreading the SARS CoV-2 corona virus world-wide is now showing anecdotal evidence of psychoses newly developing post viral exposure, implicating neuronal inflammation in crucial areas of the brain that could initiate psychotic symptoms. Time will tell if epidemiological data will, similar to the 1918 influenza pandemic, show that schizophrenia spectrum disorders increase after serious viral infections.

The association between exposure to herpes simplex virus type 1 (HSV-1) and cognitive functioning in schizophrenia: A meta-analysis.

Cognitive deficits are characteristic of schizophrenia but their etiology is not understood. Previous studies show an association between viral exposures and cognitive impairment. This meta-analysis was undertaken to determine the relationship of herpes simplex virus type 1 (HSV-1) exposure and cognitive functioning in schizophrenia. A systematic search was performed for studies comparing the cognitive functioning of HSV-1 seropositive vs. seronegative persons with schizophrenia. The primary outcome was the standardized mean difference (SMD) in composite cognitive score using Hedges' g. Secondary outcomes were SMDs in 9cognitive domains. Study heterogeneity was estimated using the I2 index and formal tests of heterogeneity using Cochran's Q. In a sample of 3516 individuals from 9 studies the SMD was negative for the composite score and all 9 domains indicating a significant deficit for seropositive individuals in 8 domains. The SMDs ranged from -0.11 (Working Memory) to -0.36 (Visual Spatial). Cochran's Q test indicated heterogeneity for one domain. The I2 index of heterogeneity was in the low -moderate range for all but one domain. Exposure to HSV-1 is associated with decreased cognitive functioning in schizophrenia. An increased understanding of HSV-1 exposure might lead to improved methods for the prevention and treatment of cognitive deficits in schizophrenia.

Schizophrenia and COVID-19 delirium.

Since its outbreak, coronavirus disease 2019 has been producing atypical manifestations aside from fever, coughing and dysnea. One of the most common is delirium, which, however, is highly overlooked. This has consequences in the treatment of patients and also may lead to underdiagnosing the infection. In this work, we present the case of a man diagnosed with schizophrenia, who had been stable for more than 20 years and that presented with an atypical picture of psychotic and confusional symptoms related to COVID-19 infection.

Can in utero Zika virus exposure be a risk factor for schizophrenia in the offspring?

Objectives: Schizophrenia is a severe psychiatric illness that has been purported to be causally related to in utero infection of neurotropic organisms. For obvious ethical reasons, this hypothesis has never been tested prospectively in humans. However, with the recent introduction of Zika virus into the New World offers the opportunity to test the hypothesis of infection in schizophrenia.Methods: This is a directed review examining the hypothesis. The literature relevant to Zika virus transmission in the New World, its biology and neurotropy is reviewed.Results: Zika virus has been associated with a wide variety of neural tube and neuroanatomical abnormalities. In its original range, Zika is only infrequently associated with congenital anomalies, but in the New World, where the majority of the population has not developed immunity, infections are associated with a wide range of neurologic abnormalities.Conclusions: The current outbreak of Zika virus in the Western Hemisphere, offers the opportunity to prospectively examine the congenital infection hypothesis of the pathogenesis of schizophrenia.

Endogenous Retroviruses Activity as a Molecular Signature of Neurodevelopmental Disorders.

Human endogenous retroviruses (HERVs) are genetic elements resulting from relics of ancestral infection of germline cells, now recognized as cofactors in the etiology of several complex diseases. Here we present a review of findings supporting the role of the abnormal HERVs activity in neurodevelopmental disorders. The derailment of brain development underlies numerous neuropsychiatric conditions, likely starting during prenatal life and carrying on during subsequent maturation of the brain. Autism spectrum disorders, attention deficit hyperactivity disorders, and schizophrenia are neurodevelopmental disorders that arise clinically during early childhood or adolescence, currently attributed to the interplay among genetic vulnerability, environmental risk factors, and maternal immune activation. The role of HERVs in human embryogenesis, their intrinsic responsiveness to external stimuli, and the interaction with the immune system support the involvement of HERVs in the derailed neurodevelopmental process. Although definitive proofs that HERVs are involved in neurobehavioral alterations are still lacking, both preclinical models and human studies indicate that the abnormal expression of ERVs could represent a neurodevelopmental disorders-associated biological trait in affected individuals and their parents.

A model of human endogenous retrovirus (HERV) activation in mental health and illness.

Despite strong evidence for the heritability of major depressive disorder (MDD), efforts to identify causal genes have been disappointing. Furthermore, although there is strong support for life stress as a major predictor of MDD, there are also considerable individual differences in susceptibility and resilience that remain poorly understood. Efforts to identify specific gene-by-environment risk factors produced results that were initially encouraging, but that were not supported by later large-scale studies. Here I propose a novel mechanism that could address the "missing heritability" of MDD, the role of environmental risk factors, and individual differences in susceptibility and resilience. This mechanism focuses on a class of transposable elements, Human Endogenous Retroviruses (HERVs), which make up approximately 8% of the human genome as the result of ancient retroviral infections that entered mammalian germ lines throughout the course of evolution. My primary hypothesis is that exposure to either exogenous viruses or traumatic experiences can activate HERVs in the brain to cause depressive (and possibly other psychiatric) symptoms. My secondary hypothesis is that individual differences in vulnerability or resilience result from the balance of activated HERVs with pathogenic versus protective functions in the brain. Future research can test these hypotheses by analysis of postmortem human brain tissue from donors with known viral or trauma histories; animal studies manipulating HERV expression; cell culture studies examining regulatory mechanisms of HERV expression; and from brain imaging studies of individuals with known HERV-expression. Such research may reveal novel functions of HERVs in neural tissue and may lead to a new generation of psychiatric interventions designed to target aberrant HERV activation.

Transcription of human endogenous retroviruses in human brain by RNA-seq analysis.

BACKGROUND: Human endogenous retroviruses (HERV) comprise 8% of the human genome and can be classified into at least 31 families. Increased levels of transcripts from the W and H families of HERV have been observed in association with human diseases, such as multiple sclerosis and schizophrenia. Although HERV transcripts have been detected in many tissues and cell-types based on microarray and PCR studies, the extent of HERV expression in different cell-types and diseases state has been less comprehensively studied. RESULTS: We examined overall transcription of HERV, and particularly of HERV-W and HERV-H elements in human postmortem brain samples obtained from individuals with psychiatric diagnoses (n = 111) and healthy controls (n = 51) by analyzing publicly available RNA sequencing datasets. Sequence reads were aligned to prototypical sequences representing HERV, downloaded from Repbase. We reported a consistent expression (0.1~0.2% of mappable reads) of different HERV families across three regions of human brains. Spearman correlations revealed highly correlated expression levels between three brain regionsacross 475 consensus sequences. By mapping sequences that aligned to the consensus sequences of HERV-W and HERV-H families to individual loci on chromosome 7, more than 60 loci from each family were identified, part of which are being transcribed. The ERVWE1, locus located at chr7q21.2, exhibited high levels of transcription across the three datasets. Notably, we demonstrated a trend of increased expression of overall HERV, as well as HERV-W family in samples from both schizophrenia and bipolar disorder patients. CONCLUSIONS: The current analyses indicate that RNA sequencing is a useful approach for investigating global expression of repetitive elements, such as HERV, in the human genome. HERV-W/H with the tendency of transcription up-regulation in patients suggests potential implication of HERV-W/H in psychiatric diseases.

Assessment of cognitive impairment in HSV-1 positive schizophrenia and bipolar patients: Systematic review and meta-analysis.

A common characteristic among schizophrenia and bipolar disorder patients is cognitive dysfunction, especially for memory and attention. Recent evidence has suggested that cognitive impairment in schizophrenia and bipolar disorder patients could be associated with herpes simplex virus 1 (HSV-1) infection, due to the ability of HSV-1 to infect neurons in the temporal lobe, which plays a key role in the formation of memory and processing of sensory input. The objective of this review is to analyze the aggregate neuropsychological testing data from previous studies regarding the impact of HSV-1 infection on cognitive function in schizophrenia and bipolar disorder. A systematic literature search generated a total of 379 articles; 12 full-text case control and cross-sectional studies met the eligibility criteria to be included in the review. Pooled effects assessed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scores and the three index scores for immediate memory, delayed memory, and attention in a random effects model. The overall effect for RBANS total score was in favor of the HSV-1 positive group (z = 3.10, p = 0.002). A statistically significant overall effect of cognitive impairment for memory and attention indices was in favor of HSV positive schizophrenia patients (z = 5.95 p < 0.00001). The findings from the meta-analysis suggest that serological evidence of HSV-1 infection has a significant impact on cognitive function with small to moderate effect sizes (-0.23 to -0.49), particularly affecting memory and attention, in schizophrenia and bipolar patients.

Nothing to sneeze at - uptake of protective measures against an influenza pandemic by people with schizophrenia: willingness and perceived barriers.

OBJECTIVES: To examine willingness to adopt protective behaviours, and perceived barriers, during a pandemic influenza, in people with schizophrenia. METHODS: A cross-sectional study using a questionnaire was conducted exploring the responses of 71 adults with schizophrenia and 238 adults without schizophrenia attending a general practice setting, regarding willingness and perceived barriers to adopting protective measures against the 2009 swine influenza pandemic in Australia. RESULTS: The majority of participants with schizophrenia reported that they would be at least moderately willing to be vaccinated (74.2%), isolate themselves (73.2%), wear a face mask (54.9%) and increase hand washing (88.6%). However, 71.8% were concerned about "catching" flu from vaccination. Predictors of willingness to adopt protective actions included self-efficacy (vaccination, face mask, isolation), perceived likelihood of contracting swine flu (vaccination), educational status (face mask) and perceived overall risk from swine flu (face mask). Key modifiable perceived barriers to adopting protective measures were identified, including cost and need for transport assistance for vaccination. CONCLUSIONS: People with schizophrenia report being generally willing to adopt protective measures, especially increased hand washing, during a pandemic influenza. Understanding perceived barriers may enable development of effective interventions to increase uptake of protective measures.

Herpes simplex virus 1 infection and valacyclovir treatment in schizophrenia: Results from the VISTA study.

BACKGROUND: Several studies have implicated herpes simplex virus-type 1 (HSV-1) in the pathophysiology of schizophrenia. A recent trial demonstrated that the anti-viral medication valacylovir, which prevents replication of activated HSV-1, improved selected cognitive deficits in people with schizophrenia. In this study, we examined demographic and illness related differences between HSV-1 positive versus HSV-1 negative subjects with early phase schizophrenia and attempted to replicate the previous valacyclovir treatment results in this population. METHODS: 170 subjects with schizophrenia (HSV-1 positive N = 70; HSV-1 negative N = 96) from 12 US sites participated in the HSV-1 positive versus negative comparisons, and were randomized 1:1 to valacyclovir (1.5 g BID) or placebo for a 16-week, double-blind efficacy trial. The primary endpoints were working and verbal memory. RESULTS: The HSV-1 positive group, as compared to the HSV-1 negative group, were older (p < 0.001) with fewer males (p = 0.003), and had a longer duration of illness (p = 0.008), more positive symptoms (p = 0.013), poorer quality of life (p = 0.034) and more impairment on the letter-number sequencing test, which is a measure of working memory (p = 0.045). Valacyclovir failed to significantly improve any of the cognitive indices, symptom or functioning measures. CONCLUSIONS: HSV-1 sero-positivity appears to be a marker of a subgroup with a more severe form of schizophrenia. Valacyclovir was not efficacious in the study, perhaps because the herpes virus was in the dormant, non-activated state and therefore non-responsive to valacyclovir effects. ClinicalTrials.gov Identifier: NCT02008773.

HERV-W env regulates calcium influx via activating TRPC3 channel together with depressing DISC1 in human neuroblastoma cells.

The activation and involvement of human endogenous retroviruses W family envelope gene (HERV-W env, also called ERVWE1) have been reported in several neuropsychiatric disorders, including schizophrenia, as well as in multiple sclerosis (MS). Dysregulation of intracellular calcium content is also involved in the pathogenesis of these diseases. Our previous studies showed that HERV-W env overexpression results in activation of small conductance Ca2+-activated K+ channel protein 3 (SK3), a potential risk factor for schizophrenia. In the present study, we aimed to elucidate the relationship between HERV-W env and calcium signaling in schizophrenia. Our results showed that HERV-W env could induce Ca2+ influx in two human neuroblastoma cell lines and upregulate the expression and activation of TRPC3 in cells. The abnormal increase in intracellular Ca2+ concentration was inhibited by addition of the TRPC3 channel blocker pyr3, demonstrating that the Ca2+ influx induced by HERV-W env was TRPC3-dependent. Further experiments showed that HERV-W env overexpression downregulated DISC1, while knockdown of DISC1 promoted activation of TRPC3 without affecting TRPC3 expression. In conclusion, HERV-W env induced Ca2+ influx in human neuroblastoma cells by activating the TRPC3 channel through directly regulating its expression or downregulating DISC1, which could also increase TRPC3 activation without affecting TRPC3 expression. These findings provide new insights into how HERV-W env affects neuronal activity and contributes to the pathogenesis of schizophrenia.

The association between Borna Disease Virus and schizophrenia: A systematic review and meta-analysis.

INTRODUCTION: Schizophrenia is a disabling psychiatric disorder. The role of Borna Disease Virus (BDV) in the etiology of schizophrenia has been suggested by several studies. However, the existence of such association remained controversial. The present meta-analysis was conducted to evaluate this association. METHOD: This systematic review and meta-analysis was conducted using preferred reporting items for systematic reviews and meta-analysis (PRISMA). Online databases including Scopus, PubMed, Science direct, Embase, PsycINFO, Web of Science and Google scholar search engine were searched until January 15, 2017. The heterogeneity of the studies was evaluated using Cochran's Q test and I2 statistic. Finally, random effects model was used for combining the results using Stata software version 11.1. RESULT: Overall, 30 studies containing 2533 cases and 4004 controls were included in the meta-analysis. The combined odds ratio (OR) for the relationship between BDV and schizophrenia was estimated to be 2.72 (95%CI: 1.75-4.20). This association based on RT-PCR, WB, IFA, EIA, RLA, ECLIA methods was estimated to be 3.83 (95%CI: 1.59-9.20), 4.99 (95%CI: 1.80-13.85), 1.27 (95%CI: 0.23-7.12), 2.26 (95%CI: 0.48-10.64), 1.67 (95%CI: 0.50-5.56) and 2.88 (95%CI: 1.38-6.01), respectively. Subgroup analysis according to WBC, serum and plasma samples was estimated to be 3.31 (95%CI: 1.19-9.25), 2.21 (95% CI: 1.17-4.17), 2.21 (95%CI: 1.03-4.73) and 7.89 (95%CI: 1.75-35.53), respectively. CONCLUSION: The results indicated the role of BDV in the etiology of schizophrenia.

Determining the IgM and IgG antibodies titer against HSV1, HSV2 and CMV in the serum of schizophrenia patients.

Schizophrenia is a destructive clinical syndrome with diverse mental pathologies. Different mechanisms and factors have a role in this disease. A possible mechanism is that teratogenic viruses cause brain changes and results in the disease appearance. The schizophrenia patients were diagnosed by psychologists and with the consent of patients, five CC of venous blood was drawn. Than Serum samples were isolated and immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against herpes simplex virus-1 (HSV-1), herpes simplex virus-2 (HSV-2) and cytomegalovirus (CMV) were quantified by ELISA sandwich kit. The Results showed that anti-CMV and anti-HSV1 and anti-HSV2 IgG antibodies in schizophrenia patients were increased significantly (p< 0.05). The increasing of the anti-HSV2 IgM was also observed but increasing amount of the anti-HSV1 IgM was not statistically significant (p< 0.05). Therefore, as a result of this study CMV and HSV1 and HSV2 infection can probably intensify the symptoms in schizophrenia patients.

[Implication of human endogenous retroviruses in schizophrenia and bipolar disorder]. / Les rétrovirus endogènes humains, une implication dans la schizophrénie et le trouble bipolaire.

Schizophrenia and bipolar disorder are neuropsychiatric disorders of unknown origin. It seems that these two disorders share some common etiopathogenic mechanisms including genetic, environmental and inflammatory ones. Reactivation of the human endogenous retrovirus type W (HERV-W) can be a shared element in the pathophysiology of schizophrenia and bipolar disorder, linked to immuno-genetic and environment risk factors. We will present studies that have highlighted the presence of HERV-W in schizophrenic and bipolar disorder patients. We will then describe a two-hit model which could explain the common pathophysiological mechanism of affective and non-affective psychosis. Identification of immuno-inflammatory mediated subgroup of schizophrenia and bipolar disorder associated to HERV-W reactivation might open the way for the development of diagnostic biomarker and more targeted treatments. These new tools pave the way towards personalized psychiatry for a better care of patients.

Cooccurrences of Putative Endogenous Retrovirus-Associated Diseases.

At least 8% of the human genome is composed of endogenous retrovirus (ERV) sequences. ERVs play a role in placental morphogenesis and can sometimes protect the host against exogenous viruses. On the other hand, ERV reactivation has been found to be associated with different diseases, for example, multiple sclerosis (MS), schizophrenia, type 1 diabetes mellitus (T1D), or amyotrophic lateral sclerosis (ALS). Little is known about the cooccurrence of these diseases. If all these diseases are caused by ERV, antiretroviral therapy should perhaps also show some effects in the other diseases. Here, we summarize literature demonstrating that some ERV-associated diseases seem to appear together more often than expected, for example, MS and ALS, MS and T1D, MS and schizophrenia, or ALS and T1D. In contrast, some ERV-associated diseases seem to appear together less frequently than expected, for example, schizophrenia and T1D. Besides, some reports demonstrate amelioration of MS, ALS, or schizophrenia under antiretroviral therapy in human immunodeficiency virus-infected patients. If such results could be confirmed in larger studies, alternative therapy strategies for ERV-associated diseases like MS and schizophrenia might be possible.