Imbalanced Oxidative Stress Causes Chlamydial Persistence during Non-Productive Human Herpes Virus Co-Infection

Prusty, Bhupesh K.; Böhme, Linda; Bergmann, Birgit; Siegl, Christine; Krause, Eva; Mehlitz, Adrian; Rudel, Thomas

doi:10.1371/journal.pone.0047427

Cited by 62 publications

(65 citation statements)

References 57 publications

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“…In contradiction, other reports have shown that HHV6 infection upregulates the levels of pro-inflammatory cytokines, such as IL-1β, TNFα, and IFNγ in peripheral blood mononuclear cells [89,90]. The latter effects may well explain why HHV6 infections are associated with dramatically elevated cellular levels of oxidative stress [91]. A combination of elevated inflammatory cytokines and oxidative stress induces mitochondrial dysfunction [29].…”

Section: Human Herpes Virusmentioning

confidence: 90%

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

Morris¹,

Berk

Walder

et al. 2015

Mol Neurobiol

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Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

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Section: Human Herpes Virusmentioning

confidence: 90%

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

Morris¹,

Berk

Walder

et al. 2015

Mol Neurobiol

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“…HeLa cells containing latent HHV-6, HSB-2 and Molt-3 cells [23] were grown in RPMI 1640 media and 5% fetal bovine serum (FBS) at 37°C and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

“…Although C. trachomatis and C. pneumoniae differ in their tissue tropism, they have a similar infection physiology. In a previous study, we have shown that co-infection with HHV-6 influences the development of infectious progeny of both, C. trachomatis and C. pneumoniae [23]. Moreover, different herpes viruses like herpes simplex virus (HSV)-1 and HSV-2 and human cytomegalovirus influence chlamydial infectivity in a similar way [23].…”

Section: Introductionmentioning

confidence: 99%

Chlamydia trachomatis Infection Induces Replication of Latent HHV-6

et al. 2013

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Human herpesvirus-6 (HHV-6) exists in latent form either as a nuclear episome or integrated into human chromosomes in more than 90% of healthy individuals without causing clinical symptoms. Immunosuppression and stress conditions can reactivate HHV-6 replication, associated with clinical complications and even death. We have previously shown that co-infection of Chlamydia trachomatis and HHV-6 promotes chlamydial persistence and increases viral uptake in an in vitro cell culture model. Here we investigated C. trachomatis-induced HHV-6 activation in cell lines and fresh blood samples from patients having Chromosomally integrated HHV-6 (CiHHV-6). We observed activation of latent HHV-6 DNA replication in CiHHV-6 cell lines and fresh blood cells without formation of viral particles. Interestingly, we detected HHV-6 DNA in blood as well as cervical swabs from C. trachomatis-infected women. Low virus titers correlated with high C. trachomatis load and vice versa, demonstrating a potentially significant interaction of these pathogens in blood cells and in the cervix of infected patients. Our data suggest a thus far underestimated interference of HHV-6 and C. trachomatis with a likely impact on the disease outcome as consequence of co-infection.

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“…P53 is known to inhibit the PPP which is important for the production of NADPH and nucleotide precursors (Jiang et al 2011). All Chlamydia depend on the host cell pool of NADPH (Prusty et al 2012) and nucleotide precursors and therefore p53-mediated shutdown of the PPP results in block of bacterial growth (Siegl et al 2014). Glucose-6-phosphate dehydrogenase (G6PD) is the first enzyme in the PPP and the major target of p53.…”

Section: Depletion Of P53mentioning

confidence: 99%

Subversion of Cell-Autonomous Host Defense by Chlamydia Infection

Fischer

Rudel

2016

Biology of Chlamydia

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Obligate intracellular bacteria entirely depend on the metabolites of their host cell for survival and generation of progeny. Due to their lifestyle inside a eukaryotic cell and the lack of any extracellular niche, they have to perfectly adapt to compartmentalized intracellular environment of the host cell and counteract the numerous defense strategies intrinsically present in all eukaryotic cells. This so-called cell-autonomous defense is present in all cell types encountering Chlamydia infection and is in addition closely linked to the cellular innate immune defense of the mammalian host. Cell type and chlamydial species-restricted mechanisms point a long-term evolutionary adaptation that builds the basis of the currently observed host and cell-type tropism among different Chlamydia species. This review will summarize the current knowledge on the strategies pathogenic Chlamydia species have developed to subvert and overcome the multiple mechanisms by which eukaryotic cells defend themselves against intracellular pathogens.

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Imbalanced Oxidative Stress Causes Chlamydial Persistence during Non-Productive Human Herpes Virus Co-Infection

Cited by 62 publications

References 57 publications

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

Chlamydia trachomatis Infection Induces Replication of Latent HHV-6

Subversion of Cell-Autonomous Host Defense by Chlamydia Infection

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