Chlamydia trachomatis Infection Induces Replication of Latent HHV-6

Prusty, Bhupesh K.; Siegl, Christine; Hauck, Petra; Hain, Johannes; Korhonen, Suvi; Hiltunen-Back, Eija; Puolakkainen, Mirja; Rudel, Thomas

doi:10.1371/journal.pone.0061400

Cited by 25 publications

(29 citation statements)

References 50 publications

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“…Chlamydia trachomatis infections as well as different drugs have been shown to be able to trigger HHV-6 reactivation [8,24]. However, they were not detectable in all and at every time-point of testing.…”

Section: Discussionmentioning

confidence: 99%

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Detection of HHV-6-specific mRNA and antigens in PBMCs of individuals with chromosomally integrated HHV-6 (ciHHV-6)

Strenger

Caselli

Lautenschlager

et al. 2014

Clinical Microbiology and Infection

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After inheritance of chromosomally integrated HHV-6 (ciHHV-6), viral DNA is found in every nucleated cell. The prevalence of ciHHV-6 is estimated to be 0.2-5% of humans. There are conflicting data on the potential for replication, possibly leading to clinical implications. We analysed peripheral blood mononuclear cells (PBMCs) from individuals with ciHHV-6 proven by fluorescence in situ hybridization (FISH) for HHV-6-specific mRNA (U94, U42, U22) and antigens by means of reverse transcription PCR and an indirect immunoperoxidase staining. U94 transcripts indicative of latent infection were detected in six (54.5%) out of 11 individuals at least once. Transcripts indicative of lytic infection (i.e. U42 and U22) were detected in four (36.4%) out of 11 individuals at least once. HHV-6 antigen was detected in seven (70%) out of 10 individuals at least once. The presence of viral mRNA and proteins supports virus gene expression from ciHHV-6, which may lead to virus replication. Considering the properties of active HHV-6 infection together with obvious replicative activity in individuals with ciHHV-6, pathophysiological effects leading to clinical consequences of chromosomally integrated viral DNA might be considered.

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Section: Discussionmentioning

confidence: 99%

“…This may indicate a differential viral activity within a time course of the same individual. Chlamydia trachomatis infections as well as different drugs have been shown to be able to trigger HHV-6 reactivation [8,24]. Exogenous factors might play a role even in activation of ciHHV-6.…”

Section: Discussionmentioning

confidence: 99%

Detection of HHV-6-specific mRNA and antigens in PBMCs of individuals with chromosomally integrated HHV-6 (ciHHV-6)

Strenger

Caselli

Lautenschlager

et al. 2014

Clinical Microbiology and Infection

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“…Such co-infections occur frequently between several bacterial pathogens and certain viruses, such as Streptococcus spp. and influenza virus (Chertow and Memoli, 2013), Trichomonas vaginalis and human immunodeficiency virus (Kissinger and Adamski, 2013) or Chlamydia trachomatis and human herpes virus (Prusty et al, 2013). The genome-independent nature of RNA-seq again bears great potential to analyze gene expression changes of the host together with those of its multiple pathogens.…”

Section: Bacterial/viral Co-infectionsmentioning

confidence: 99%

Dual RNA-seq of pathogen and host

2012

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SummaryThe infection of a eukaryotic host cell by a bacterial pathogen is one of the most intimate examples of cross-kingdom interactions in biology. Infection processes are highly relevant from both a basic research as well as a clinical point of view. Sophisticated mechanisms have evolved in the pathogen to manipulate the host response and vice versa host cells have developed a wide range of anti-microbial defense strategies to combat bacterial invasion and clear infections.However, it is this diversity and complexity that makes infection research so challenging to technically address as common approaches have either been optimized for bacterial or eukaryotic organisms. Instead, methods are required that are able to deal with the often dramatic discrepancy between host and pathogen with respect to various cellular properties and processes. One class of cellular macromolecules that exemplify this host-pathogen heterogeneity is given by their transcriptomes: Bacterial transcripts differ from their eukaryotic counterparts in many aspects that involve both quantitative and qualitative traits. The entity of RNA transcripts present in a cell is of paramount interest as it reflects the cell's physiological state under the given condition. Genome-wide transcriptomic techniques such as RNA-seq have therefore been used for single-organism analyses for several years, but their applicability has been limited for infection studies.The present work describes the establishment of a novel transcriptomic approach for infection biology which we have termed "Dual RNA-seq". Using this technology, it was intended to shed light particularly on the contribution of non-protein-encoding transcripts to virulence, as these classes have mostly evaded previous infection studies due to the lack of suitable methods. The performance of Dual RNA-seq was evaluated in an in vitro infection model based on the important facultative intracellular pathogen Salmonella enterica serovar Typhimurium and different human cell lines. Dual RNA-seq was found to be capable of capturing all major bacterial and human transcript classes and proved reproducible. During the course of these experiments, a previously largely uncharacterized bacterial small non-coding RNA (sRNA), referred to as STnc440, was identified as one of the most strongly induced genes in intracellular Salmonella.Interestingly, while inhibition of STnc440 expression has been previously shown to cause a virulence defect in different animal models of Salmonellosis, the underlying molecular mechanisms have remained obscure. Here, classical genetics, transcriptomics and biochemical assays proposed a complex model of Salmonella gene expression control that is orchestrated by this sRNA. In particular, STnc440 was found to be involved in the regulation of multiple bacterial target mRNAs by direct base pair interaction with consequences for Salmonella virulence and

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“…Such short, unstable telomeres are thought to facilitate excision of viral genomes via telomere-loops within the viral genome [43]. Interestingly, Chlamydia trachomatis drives reactivation of ciHHV-6 and transient shortening of telomere ends [45]; the signaling pathways and mechanism of excision remain to be defined.…”

Section: Latency and Reactivationmentioning

confidence: 99%

Roseolovirus molecular biology: recent advances

Krug

Pellett

2014

Current Opinion in Virology

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Human herpesviruses 6A, −6B, and −7 (HHV-6A, −6B, and −7) are classified within the roseolovirus genus of the betaherpesvrus subfamily. Most humans likely harbor at least two of these large DNA viruses, and 1% of humans harbor germline chromosomally integrated HHV-6A or HHV-6B genomes. Differences at the genetic level manifest as distinct biologic properties during infection and disease. We provide a brief synopsis of roseolovirus replication and highlight the unique properties of their lifecycle and what is known about the viral gene products that mediate these functions. In the nearly 30 years since their discovery, we have only begun to unlock the molecular strategies these highly evolved pathogens employ to establish and maintain chronic infections in humans.

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Chlamydia trachomatis Infection Induces Replication of Latent HHV-6

Cited by 25 publications

References 50 publications

Detection of HHV-6-specific mRNA and antigens in PBMCs of individuals with chromosomally integrated HHV-6 (ciHHV-6)

Detection of HHV-6-specific mRNA and antigens in PBMCs of individuals with chromosomally integrated HHV-6 (ciHHV-6)

Dual RNA-seq of pathogen and host

Roseolovirus molecular biology: recent advances

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