Viruses in neurodegenerative diseases: More than just suspects in crimes

Abstract

Neurodegenerative diseases (NDs) such as Alzheimer’s and Parkinson’s disease are fatal neurological diseases that can be of idiopathic, genetic, or even infectious origin, as in the case of transmissible spongiform encephalopathies. The etiological factors that lead to neurodegeneration remain unknown but likely involve a combination of aging, genetic risk factors, and environmental stressors. Accumulating evidence hints at an association of viruses with neurodegenerative disorders and suggests that virus-induced neuroinflammation and perturbation of neuronal protein quality control can be involved in the early steps of disease development. In this review, we focus on emerging evidence for a correlation between NDs and viral infection and discuss how viral manipulations of cellular processes can affect the formation and dissemination of disease-associated protein aggregates.

Biomolecular condensates: insights into early and late steps of the HIV-1 replication cycle

“…Future perspectives for HIV-1 will include the study on how condensation plays roles in early pre-integration, integration steps [34,75,90] as well late in HIV-1 replication in transcription, considering that recently characterized BMCs involving host histone chaperone chromatin assembly factor 1 and polycomb repressive complex 1 and their influence on HIV-1 reactivation from latency, acting near the HIV-1 promoter [102,134]. Targeting viruses with BMC therapeutics will be multi-pronged since virus infection, including HIV-1, exacerbates the outcomes of neurodegenerative a Mostly ordered proteins are those found in the dark blue and light blue areas of the mean disorder score (MDS) vs. percent of predicted intrinsically disordered residues (PPIDR) plots; i.e., areas containing proteins with PPIDR < 10% and MDS < 0.15, where dark blue correspond to area where these two parameters agree (upper values in the corresponding cells), whereas light blue color show areas in which only one of these criteria applies (bottom values in the corresponding cells) b Moderately disordered proteins are those found in the dark pink and light pink areas of the mean disorder score (MDS) vs. percent of predicted intrinsically disordered residues (PPIDR) plots; i.e., areas containing proteins with 10% ≤ PPIDR < 30% and 0.15 ≤ MDS < 0.1, where dark pink correspond to the area where these two parameters agree (upper values in the corresponding cells), whereas light pink color show areas, in which only one of these criteria applies (bottom values in the corresponding cells) c Mostly disordered proteins are those found in the red area of the mean disorder score (MDS) vs. percent of predicted intrinsically disordered residues (PPIDR) plots; i.e., area containing proteins with PPIDR ≥ 30% and MDS ≥ 0. diseases that are often dependent on BMC assemblies [135,136].…”

Brain Virome in Neurodegenerative Disorders: Insights from Transcriptomic Data Analysis

“…1 It is well known that certain viruses can infect and spread to neurons, thereby causing neuronal cell death. 2,3 Some could trigger chronic illnesses like AD, where latent infections may reappear after remaining unnoticed for years. 4 Findings, which point to a link between systemic inflammation, neurodegeneration, and the specific pathological features of NDs, may have significant repercussions for a sizable portion of the adult population, even those who appear to be in generally good health.…”

“…11,12 NDs, in turn, may modify the brain in ways that affect how the body responds to viral infections. 2 For instance, AD patients are more susceptible to viral infections, such as influenza and pneumonia. 13 Viral infections can alter the fate of ND-related proteins by dysregulating intracellular trafficking, increasing local concentrations, lowering thermodynamic barriers for aggregation, and impairing protein clearance in the cell.…”

“…Recent research has raised the possibility that viruses play an important role in the emergence of neurodegenerative disorders (NDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) . It is well known that certain viruses can infect and spread to neurons, thereby causing neuronal cell death. , Some could trigger chronic illnesses like AD, where latent infections may reappear after remaining unnoticed for years . Findings, which point to a link between systemic inflammation, neurodegeneration, and the specific pathological features of NDs, may have significant repercussions for a sizable portion of the adult population, even those who appear to be in generally good health .…”

Enterovirus infection and its relationship with neurodegenerative diseases

“…Numerous studies on NDs and pathogenic organisms have been conducted in recent years, and viruses have mostly been reported as risk factors for the development of neurodegeneration and dementia. 7 , 8 , 9 , 10 Additionally, emerging evidence suggests that alterations induced in the gut microbiome may play a significant role in the development of NDs. For instance, many viral infections can cause a microbiome-gut-brain axis imbalance (dysbiosis) and are associated with neurodegeneration either directly (through viral infection on neural cells) or indirectly [as the viral infection may trigger a systemic inflammation by increasing gut permeability, which may increase levels of circulating lipopolysaccharides causing the release of inflammatory cytokines in the central nervous system (CNS)].…”