HSV-1 and Alzheimerâ€™s disease: more than a hypothesis

Piacentini, Roberto; Chiara, Giovanna De; Puma, Domenica Donatella Li; Ripoli, Cristian; Marcocci, Maria Elena; Garaci, Enrico; Palamara, Anna Teresa; Grassi, Claudio

doi:10.3389/fphar.2014.00097

Cited by 93 publications

(103 citation statements)

References 100 publications

(123 reference statements)

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“…The majority of the population are infected with HSV-1, which is largely responsible for oral cold sores; however, in rarer cases, it can cause severe conditions, such as blindness and encephalitis (3,4). Recent experimental and epidemiological evidence also suggests a role for recurrent HSV-1 infection in Alzheimer's disease (5). Despite its clear medical significance, the relationship between the virus and its host cells is complex and is still not fully understood.…”

mentioning

confidence: 99%

Infection by Herpes Simplex Virus 1 Causes Near-Complete Loss of RNA Polymerase II Occupancy on the Host Cell Genome

Abrisch

Eidem

Yakovchuk

et al. 2016

J Virol

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Lytic infection by herpes simplex virus 1 (HSV-1) triggers a change in many host cell programs as the virus strives to express its own genes and replicate. Part of this process is repression of host cell transcription by RNA polymerase II (Pol II), which also transcribes the viral genome. Here, we describe a global characterization of Pol II occupancy on the viral and host genomes in response to HSV-1 infection using chromatin immunoprecipitation followed by deep sequencing (ChIP-seq). The data reveal near-complete loss of Pol II occupancy throughout host cell mRNA genes, in both their bodies and promoter-proximal regions. Increases in Pol II occupancy of host cell genes, which would be consistent with robust transcriptional activation, were not observed. HSV-1 infection induced a more potent and widespread repression of Pol II occupancy than did heat shock, another cellular stress that widely represses transcription. Concomitant with the loss of host genome Pol II occupancy, we observed Pol II covering the HSV-1 genome, reflecting a high level of viral gene transcription. Interestingly, the positions of the peaks of Pol II occupancy at HSV-1 and host cell promoters were different. The primary peak of Pol II occupancy at HSV-1 genes is ϳ170 bp upstream of where it is positioned at host cell genes, suggesting that specific steps in transcription are regulated differently at HSV-1 genes than at host cell mRNA genes. IMPORTANCE We investigated the effect of herpes simplex virus 1 (HSV-1) infection on transcription of host cell and viral genes by RNA polymerase II (Pol II). The approach we used was to determine how levels of genome-bound Pol II changed after HSV-1 infection.We found that HSV-1 caused a profound loss of Pol II occupancy across the host cell genome. Increases in Pol II occupancy were not observed, showing that no host genes were activated after infection. In contrast, Pol II occupied the entire HSV-1 genome. Moreover, the pattern of Pol II at HSV-1 genes differed from that on host cell genes, suggesting a unique mode of viral gene transcription. These studies provide new insight into how HSV-1 causes changes in the cellular program of gene expression and how the virus coopts host Pol II for its own use. Herpes simplex virus 1 (HSV-1) is a double-stranded DNA virus that proliferates in the nuclei of host cells during lytic infection (reviewed in reference 1). HSV-1 can cause lifelong infection by establishing asymptomatic latency in host sensory neurons, where it remains in a transcriptionally silenced state until it is stimulated by stress to reactivate and replicate in epithelial cells (2). The majority of the population are infected with HSV-1, which is largely responsible for oral cold sores; however, in rarer cases, it can cause severe conditions, such as blindness and encephalitis (3, 4). Recent experimental and epidemiological evidence also suggests a role for recurrent HSV-1 infection in Alzheimer's disease (5). Despite its clear medical significance, the relationship between the virus ...

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mentioning

confidence: 99%

Infection by Herpes Simplex Virus 1 Causes Near-Complete Loss of RNA Polymerase II Occupancy on the Host Cell Genome

Abrisch

Eidem

Yakovchuk

et al. 2016

J Virol

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“…[92][93][94] While patients rarely exhibit signs of encephalitis, many postmortem studies find a high prevalence of HSV-1 in the brain. [95][96][97][98] Strikingly, Alzheimer disease brains contain a high localization of HSV-1 DNA within amyloid plaques, 72% in AD patients, whereas only 24% of the DNA associates with plaques in agematched non-AD patients, who accumulate plaques at a much lower rate.…”

Section: Hsv-1-associated Autophagy Dysfunction: a Risk Factor For Nementioning

confidence: 99%

Autophagy interaction with herpes simplex virus type-1 infection

O’Connell

Liang

2016

Autophagy

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More than 50% of the U.S. population is infected with herpes simplex virus type-I (HSV-1) and global infectious estimates are nearly 90%. HSV-1 is normally seen as a harmless virus but debilitating diseases can arise, including encephalitis and ocular diseases. HSV-1 is unique in that it can undermine host defenses and establish lifelong infection in neurons. Viral reactivation from latency may allow HSV-1 to lay siege to the brain (Herpes encephalitis). Recent advances maintain that HSV-1 proteins act to suppress and/or control the lysosome-dependent degradation pathway of macroautophagy (hereafter autophagy) and consequently, in neurons, may be coupled with the advancement of HSV-1-associated pathogenesis. Furthermore, increasing evidence suggests that HSV-1 infection may constitute a gradual risk factor for neurodegenerative disorders. The relationship between HSV-1 infection and autophagy manipulation combined with neuropathogenesis may be intimately intertwined demanding further investigation.

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“…Accordingly, post-mortem PCR-based studies detected latent HSV-1 virus in the central nervous system (CNS) in a high percentage of brains. (for review, see Bearer, 2012;Piacentini et al, 2014). An important support for this idea was the finding that demonstrated the presence of the HSV-1 DNA in brains of individuals previously infected by the virus (Saldanha et al, 1986;Jamieson et al, 1992), which suggested that HSV-1 can establish latency in CNS neurons and possibly undergo reactivations.…”

Section: Introductionmentioning

confidence: 99%