kelly posted this to co-cure today
[if: I'd love it if one of our local science geniuses could explain any potential relevance of this for ME/CFS.]
Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5563-8. Epub 2010 Mar 8.
The latent human herpesvirus-6A genome specifically integrates in telomeres
of human chromosomes in vivo and in vitro.
Arbuckle JH, Medveczky MM, Luka J, Hadley SH, Luegmayr A, Ablashi D, Lund
TC, Tolar J, De Meirleir K, Montoya JG, Komaroff AL, Ambros PF, Medveczky
PG.
Department of Molecular Medicine, University of South Florida College of
Medicine, Tampa, FL 33612.
Previous research has suggested that human herpesvirus-6 (HHV-6) may
integrate into host cell chromosomes and be vertically transmitted in the
germ line, but the evidence-primarily fluorescence in situ hybridization
(FISH)-is indirect.
We sought, first, to definitively test these two hypotheses. Peripheral
blood mononuclear cells (PBMCs) were isolated from families in which several
members, including at least one parent and child, had unusually high copy
numbers of HHV-6 DNA per milliliter of blood. FISH confirmed that HHV-6 DNA
colocalized with telomeric regions of one allele on chromosomes 17p13.3,
18q23, and 22q13.3, and that the integration site was identical among
members of the same family. Integration of the HHV-6 genome into TTAGGG
telomere repeats was confirmed by additional methods and sequencing of the
integration site. Partial sequencing of the viral genome identified the same
integrated HHV-6A strain within members of families, confirming vertical
transmission of the viral genome.
We next asked whether HHV-6A infection of nave cell lines could lead to
integration. Following infection of nave Jjhan and HEK-293 cell lines by
HHV-6, the virus integrated into telomeres. Reactivation of integrated
HHV-6A virus from individuals' PBMCs as well as cell lines was successfully
accomplished by compounds known to induce latent herpesvirus replication.
Finally, no circular episomal forms were detected even by PCR. Taken
together, the data suggest that HHV-6 is unique among human herpesviruses:
it specifically and efficiently integrates into telomeres of chromosomes
during latency rather than forming episomes, and the integrated viral genome
is capable of producing virions.
PMID: 20212114 [PubMed - in process]
-
[if: I'd love it if one of our local science geniuses could explain any potential relevance of this for ME/CFS.]
Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5563-8. Epub 2010 Mar 8.
The latent human herpesvirus-6A genome specifically integrates in telomeres
of human chromosomes in vivo and in vitro.
Arbuckle JH, Medveczky MM, Luka J, Hadley SH, Luegmayr A, Ablashi D, Lund
TC, Tolar J, De Meirleir K, Montoya JG, Komaroff AL, Ambros PF, Medveczky
PG.
Department of Molecular Medicine, University of South Florida College of
Medicine, Tampa, FL 33612.
Previous research has suggested that human herpesvirus-6 (HHV-6) may
integrate into host cell chromosomes and be vertically transmitted in the
germ line, but the evidence-primarily fluorescence in situ hybridization
(FISH)-is indirect.
We sought, first, to definitively test these two hypotheses. Peripheral
blood mononuclear cells (PBMCs) were isolated from families in which several
members, including at least one parent and child, had unusually high copy
numbers of HHV-6 DNA per milliliter of blood. FISH confirmed that HHV-6 DNA
colocalized with telomeric regions of one allele on chromosomes 17p13.3,
18q23, and 22q13.3, and that the integration site was identical among
members of the same family. Integration of the HHV-6 genome into TTAGGG
telomere repeats was confirmed by additional methods and sequencing of the
integration site. Partial sequencing of the viral genome identified the same
integrated HHV-6A strain within members of families, confirming vertical
transmission of the viral genome.
We next asked whether HHV-6A infection of nave cell lines could lead to
integration. Following infection of nave Jjhan and HEK-293 cell lines by
HHV-6, the virus integrated into telomeres. Reactivation of integrated
HHV-6A virus from individuals' PBMCs as well as cell lines was successfully
accomplished by compounds known to induce latent herpesvirus replication.
Finally, no circular episomal forms were detected even by PCR. Taken
together, the data suggest that HHV-6 is unique among human herpesviruses:
it specifically and efficiently integrates into telomeres of chromosomes
during latency rather than forming episomes, and the integrated viral genome
is capable of producing virions.
PMID: 20212114 [PubMed - in process]
-
