Parvovirus B19 DNA CpG Dinucleotide Methylation and Epigenetic Regulation of Viral Expression

Bonvicini, Francesca; Manaresi, Elisabetta; Furio, Francesca Di; Falco, Luisa De; Gallinella, Giorgio

doi:10.1371/journal.pone.0033316

Cited by 25 publications

(20 citation statements)

References 42 publications

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“…A further level of regulation of viral expression can be at the epigenetic level [107]. In this respect, CpG DNA methylation is one of the main epigenetic modifications playing a role in the control of gene expression.…”

Section: Expression Profilementioning

confidence: 99%

“…For example, in the semipermissive UT7 cells, after a few rounds of productive replication the virus can still be detected for extended periods of time showing a progressive loss of activity [55,107], and also in nonpermissive systems such as U937 cells the viral DNA can be maintained within cells for some time in the absence of detectable viral activity [107]. These systems may mirror what happens in vivo.…”

Section: Virus Persistence Following In Vitro Infections Carrier Cumentioning

confidence: 99%

“…A possibility is that the virus might establish true latent infections, with the capability of reactivations, but this has only rarely been suggested and not fully documented. Epigenetic levels of regulation may play an important role in the control of viral expression and determining a silencing of persistent viral DNA [107]. Since effects on cell physiology would probably depend on the expression of viral proteins impacting cellular pathways, a silenced genome would not alter a cellular environment by definition.…”

Section: Virus Persistence Following In Vitro Infections Carrier Cumentioning

confidence: 99%

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Parvovirus B19 Achievements and Challenges

Gallinella

2013

ISRN Virology

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Parvovirus B19 is a widespread human pathogenic virus, member of the Erythrovirus genus in the Parvoviridae family. Infection can be associated with an ample range of pathologies and clinical manifestations, whose characteristics and outcomes depend on the interplay between the pathogenetic potential of the virus, its adaptation to different cellular environments, and the physiological and immune status of the infected individuals. The scope of this review is the advances in knowledge on the biological characteristics of the virus and of virus-host relationships; in particular, the interactions of the virus with different cellular environments in terms of tropism and ability to achieve a productive replicative cycle, or, on the contrary, to establish persistence; the consequences of infection in terms of interference with the cell physiology; the process of recognition of the virus by the innate or adaptive immune system, hence the role of the immune system in controlling the infection or in the development of clinical manifestations. Linked to these issues is the continuous effort to develop better diagnostic algorithms and methods and the need for development of prophylactic and therapeutic options for B19V infections.

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Section: Expression Profilementioning

confidence: 99%

Section: Virus Persistence Following In Vitro Infections Carrier Cumentioning

confidence: 99%

Section: Virus Persistence Following In Vitro Infections Carrier Cumentioning

confidence: 99%

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Parvovirus B19 Achievements and Challenges

Gallinella

2013

ISRN Virology

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“…In a recent report, Bonvicini et al demonstrated for the first time CpG methylation of a single-stranded DNA (ssDNA) virus (18). They showed extensive CpG methylation of parvovirus B19 both in clinical samples and in cell culture models (18). Studies demonstrating the loss of CpG dinucleotides in small DNA viruses (Ͻ30 kb) have focused only on viruses infecting humans or higher-order mammals.…”

mentioning

confidence: 99%

“…To test this hypothesis, we chose to investigate the CpG dinucleotide content of parvoviruses, which are single-stranded DNA viruses infecting a wide range of hosts, spanning from insects to primates, including humans. We believe that parvoviruses are an appropriate choice to test our hypothesis for the following reasons: (i) parvoviruses do not encode their own polymerase and their replication is dependent on the cellular replication machinery (19,20), (ii) parvoviruses are known for their rapid adaption to the host (21), (iii) recent studies on parvovirus B19 confirm that parvovirus DNA is extensively methylated in humans (18), (iv) single-stranded methylated DNA is more rapidly deaminated than double-stranded methylated DNA (22), and (v) parvoviruses spanning across different subfamilies share common ancestral origins (23). Therefore, we believe that parvoviruses are suitable to study host-driven evolution of viruses.…”

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confidence: 99%

CpG Dinucleotide Frequencies Reveal the Role of Host Methylation Capabilities in Parvovirus Evolution

Upadhyay

Samal

Kandpal

et al. 2013

J Virol

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Parvoviruses are rapidly evolving viruses that infect a wide range of hosts, including vertebrates and invertebrates. Extensive methylation of the parvovirus genome has been recently demonstrated. A global pattern of methylation of CpG dinucleotides is seen in vertebrate genomes, compared to "fractional" methylation patterns in invertebrate genomes. It remains unknown if the loss of CpG dinucleotides occurs in all viruses of a given DNA virus family that infect host species spanning across vertebrates and invertebrates. We investigated the link between the extent of CpG dinucleotide depletion among autonomous parvoviruses and the evolutionary lineage of the infected host. We demonstrate major differences in the relative abundance of CpG dinucleotides among autonomous parvoviruses which share similar genome organization and common ancestry, depending on the infected host species. Parvoviruses infecting vertebrate hosts had significantly lower relative abundance of CpG dinucleotides than parvoviruses infecting invertebrate hosts. The strong correlation of CpG dinucleotide depletion with the gain in TpG/CpA dinucleotides and the loss of TpA dinucleotides among parvoviruses suggests a major role for CpG methylation in the evolution of parvoviruses. Our data present evidence that links the relative abundance of CpG dinucleotides in parvoviruses to the methylation capabilities of the infected host. In sum, our findings support a novel perspective of host-driven evolution among autonomous parvoviruses.T he relative abundance of dinucleotides, particularly the CpG dinucleotide, has received much attention recently. The CpG dinucleotide content is normally expressed as a ratio of the actual (observed) number of CpG dinucleotides and the expected number of CpG dinucleotides (O/E ratio). The relative abundance of CpG dinucleotides varies greatly across viruses (1, 2). Depletion of CpG dinucleotides has been reported to occur in all small DNA viruses (Ͻ30 kb) infecting humans (2), while most large DNA viruses (Ͼ30 kb) infecting humans show little or no CpG dinucleotide depletion. Several possible reasons have been suggested to play a role in the depletion of CpG dinucleotides, including (i) lower transcription rate for CpG-containing codons (3), (ii) stimulation of Toll-like receptor 9-mediated innate immune response by unmethylated CpGs (4), and (iii) spontaneous deamination of methylated cytosines in CpG dinucleotides (5). Deamination of unmethylated cytosines results in C-to-U transitions which are amenable to mismatch repair mechanisms, whereas the deamination of 5-methylcytosine leads to C-to-T transitions that are often irreversible, resulting in high mutation rates in methylated CpGs and a depletion of CpG dinucleotides (6, 7).In most vertebrate genomes, the O/E ratio for CpG dinucleotides is Ͻ0.35, suggesting that vertebrate genomes have lost about two-thirds of CpG dinucleotides (5, 8). In contrast, invertebrate genomes show minor or no depletion of CpG dinucleotides (5). Early investigations on insects showed that...

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