Ecoclimber
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Genome Biol Evol. 2014 Mar 28. [Epub ahead of print]
Genome-wide analysis of wild-type Epstein-Barr virus genomes derived from healthy individuals of the 1000 Genomes Project.
Santpere G1, Darre F, Blanco S, Alcami A, Villoslada P, Albà MM, Navarro A.
Abstract
Most people in the world (~90%) are infected by the Epstein-Barr virus (EBV), which establishes itself permanently in B-cells. Infection by EBV is related to a number of diseases including infectious mononucleosis, multiple sclerosis and different types of cancer.
So far, only seven complete EBV strains have been described, all of them coming from donors presenting EBV-related diseases. To perform a detailed comparative genomics analysis of EBV including, for the first time, EBV strains derived from healthy individuals we reconstructed EBV sequences infecting lymphoblastoid cell lines (LCLs) from the 1000 Genomes Project.
Since strain B95-8 was used to transform B-cells to obtain LCLs, it is always present, but a specific deletion in its genome sets it apart from natural EBV strains. After studying hundreds of individuals, we determined the presence of natural EBV in at least 10 of them and obtained a set of variants specific to wild-type EBV.
By mapping the natural EBV reads into the EBV reference genome (NC007605) we constructed nearly complete wild-type viral genomes from three individuals. Adding them to the five disease-derived EBV genomic sequences available in the literature, we performed an in-depth comparative genomic analysis.
We found that latency genes harbour more nucleotide diversity than lytic genes and that six out of nine latency-related genes, as well as other genes involved in viral attachment and entry into host cells, packaging and the capsid, present the molecular signature of accelerated protein evolution rates, suggesting rapid host-parasite co-evolution.
KEYWORDS:
EBV, Human Herpesvirus 4, Illumina reads, recombination, selection, whole-genome analysis
For Full Free Access Click on this Link for PDF
Epub: Santpere et al. Genome-wide analysis of wild-type Epstein-Barr virus genomes derived from healthy individuals of the 1000 Genomes Project. Genome Biol Evol. 2014 Mar.
Background: Most people in the world (~90%) are infected by the Epstein-Barr virus (EBV), which establishes itself permanently in B-cells. Infection by EBV is related to a number of diseases including infectious mononucleosis, multiple sclerosis and different types of cancer. So far, only seven complete EBV strains have been described, all of them coming from donors presenting EBV-related diseases.
Aim: To perform a detailed comparative genomics analysis of EBV including, for the first time, EBV strains derived from healthy individuals we reconstructed EBV sequences infecting lymphoblastoid cell lines (LCLs) from the 1000 Genomes Project.
Methods: Since strain B95-8 was used to transform B-cells to obtain LCLs, it is always present, but a specific deletion in its genome sets it apart from natural EBV strains.
Results: After studying hundreds of individuals, we determined the presence of natural EBV in at least 10 of them and obtained a set of variants specific to wild-type EBV. By mapping the natural EBV reads into the EBV reference genome (NC007605) we constructed nearly complete wild-type viral genomes from three individuals. Adding them to the five disease-derived EBV genomic sequences available in the literature, we performed an in-depth comparative genomic analysis.
Conclusion: We found that latency genes harbour more nucleotide diversity than lytic genes and that six out of nine latency-related genes, as well as other genes involved in viral attachment and entry into host cells, packaging and the capsid, present the molecular signature of accelerated protein evolution rates, suggesting rapid host-parasite co-evolution.
What this means for MSers by Prof. Gavin Giovannoni
Permission to repost
"At last big genomics comes to EBV. Not all EBV viruses are the same; within the populations of the world different strains of EBV exist and within an individual different forms of EBV can evolve. The rapid evolution of viruses between populations and within individuals is well described for many viruses so why should EBV be any different? Why is this important?
I hypothesised several years ago that maybe the strain of EBV that triggers, or drives, MS is a different strain to that that lives and thrives in the general population. In other words for EBV to cause MS it needs to be a mutant-EBV. There are analogies to this hypothesis. Almost all the common viruses that result in chronic slow viral infections of the brain have mutant strains that do the dirty work.
This was first described for the measles virus; the strain of measles that causes subacute sclerosing panencephalitis (SSPE); the measle virus that causes SSPE has a mutation in its M protein. Similarly, the strain of herpes simplex virus that causes encephalitis has a specific mutation in its genome that allows it infect the brain. JCV that causes PML in MSers on natalizumab has several mutations in its coat protein, VP1, and a mutation in the part of its genome that regulates its function.
These examples support the hypothesis of why we should be taking a deep look into the EBV genome of MSers. Where would we look? The obvious place to look is in the blood or saliva, where the virus is found normally. However, this may the wrong compartment to look. I would suggest we take a look in the brain and cervical, or neck, lymph nodes of people with MS. This is the place we are more likely to find the mutant strain lurking. What is needed to do these studies? (1) Tissue collected in a special way from people dying with MS, (2) a new breed of scientist and (3) deep pockets."
Click on this link for further analysis.
Genome-wide analysis of wild-type Epstein-Barr virus genomes derived from healthy individuals of the 1000 Genomes Project.
Santpere G1, Darre F, Blanco S, Alcami A, Villoslada P, Albà MM, Navarro A.
Abstract
Most people in the world (~90%) are infected by the Epstein-Barr virus (EBV), which establishes itself permanently in B-cells. Infection by EBV is related to a number of diseases including infectious mononucleosis, multiple sclerosis and different types of cancer.
So far, only seven complete EBV strains have been described, all of them coming from donors presenting EBV-related diseases. To perform a detailed comparative genomics analysis of EBV including, for the first time, EBV strains derived from healthy individuals we reconstructed EBV sequences infecting lymphoblastoid cell lines (LCLs) from the 1000 Genomes Project.
Since strain B95-8 was used to transform B-cells to obtain LCLs, it is always present, but a specific deletion in its genome sets it apart from natural EBV strains. After studying hundreds of individuals, we determined the presence of natural EBV in at least 10 of them and obtained a set of variants specific to wild-type EBV.
By mapping the natural EBV reads into the EBV reference genome (NC007605) we constructed nearly complete wild-type viral genomes from three individuals. Adding them to the five disease-derived EBV genomic sequences available in the literature, we performed an in-depth comparative genomic analysis.
We found that latency genes harbour more nucleotide diversity than lytic genes and that six out of nine latency-related genes, as well as other genes involved in viral attachment and entry into host cells, packaging and the capsid, present the molecular signature of accelerated protein evolution rates, suggesting rapid host-parasite co-evolution.
KEYWORDS:
EBV, Human Herpesvirus 4, Illumina reads, recombination, selection, whole-genome analysis
For Full Free Access Click on this Link for PDF
Epub: Santpere et al. Genome-wide analysis of wild-type Epstein-Barr virus genomes derived from healthy individuals of the 1000 Genomes Project. Genome Biol Evol. 2014 Mar.
Background: Most people in the world (~90%) are infected by the Epstein-Barr virus (EBV), which establishes itself permanently in B-cells. Infection by EBV is related to a number of diseases including infectious mononucleosis, multiple sclerosis and different types of cancer. So far, only seven complete EBV strains have been described, all of them coming from donors presenting EBV-related diseases.
Aim: To perform a detailed comparative genomics analysis of EBV including, for the first time, EBV strains derived from healthy individuals we reconstructed EBV sequences infecting lymphoblastoid cell lines (LCLs) from the 1000 Genomes Project.
Methods: Since strain B95-8 was used to transform B-cells to obtain LCLs, it is always present, but a specific deletion in its genome sets it apart from natural EBV strains.
Results: After studying hundreds of individuals, we determined the presence of natural EBV in at least 10 of them and obtained a set of variants specific to wild-type EBV. By mapping the natural EBV reads into the EBV reference genome (NC007605) we constructed nearly complete wild-type viral genomes from three individuals. Adding them to the five disease-derived EBV genomic sequences available in the literature, we performed an in-depth comparative genomic analysis.
Conclusion: We found that latency genes harbour more nucleotide diversity than lytic genes and that six out of nine latency-related genes, as well as other genes involved in viral attachment and entry into host cells, packaging and the capsid, present the molecular signature of accelerated protein evolution rates, suggesting rapid host-parasite co-evolution.
What this means for MSers by Prof. Gavin Giovannoni
Permission to repost
"At last big genomics comes to EBV. Not all EBV viruses are the same; within the populations of the world different strains of EBV exist and within an individual different forms of EBV can evolve. The rapid evolution of viruses between populations and within individuals is well described for many viruses so why should EBV be any different? Why is this important?
I hypothesised several years ago that maybe the strain of EBV that triggers, or drives, MS is a different strain to that that lives and thrives in the general population. In other words for EBV to cause MS it needs to be a mutant-EBV. There are analogies to this hypothesis. Almost all the common viruses that result in chronic slow viral infections of the brain have mutant strains that do the dirty work.
This was first described for the measles virus; the strain of measles that causes subacute sclerosing panencephalitis (SSPE); the measle virus that causes SSPE has a mutation in its M protein. Similarly, the strain of herpes simplex virus that causes encephalitis has a specific mutation in its genome that allows it infect the brain. JCV that causes PML in MSers on natalizumab has several mutations in its coat protein, VP1, and a mutation in the part of its genome that regulates its function.
These examples support the hypothesis of why we should be taking a deep look into the EBV genome of MSers. Where would we look? The obvious place to look is in the blood or saliva, where the virus is found normally. However, this may the wrong compartment to look. I would suggest we take a look in the brain and cervical, or neck, lymph nodes of people with MS. This is the place we are more likely to find the mutant strain lurking. What is needed to do these studies? (1) Tissue collected in a special way from people dying with MS, (2) a new breed of scientist and (3) deep pockets."
Click on this link for further analysis.
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