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HIV infection reveals widespread expansion of novel centromeric human endogenous retroviruses

Overstressed

Senior Member
Messages
406
Location
Belgium
A very very very nice piece of science -and to no surprise- they show how HIV activates the expression of novel HERV-K provirus...:

http://genome.cshlp.org/content/23/9/1505.full

An abstract:

Human endogenous retroviruses (HERVs) make up 8% of the human genome. The HERV-K (HML-2) family is the most recent group of these viruses to have inserted into the genome, and we have detected the activation of HERV-K (HML-2) proviruses in the blood of patients with HIV-1 infection. We report that HIV-1 infection activates expression of a novel HERV-K (HML-2) provirus, termed K111, present in multiple copies in the centromeres of chromosomes throughout the human genome yet not annotated in the most recent human genome assembly. Infection with HIV-1 or stimulation with the HIV-1 Tat protein leads to the activation of K111 proviruses. K111 is present as a single copy in the genome of the chimpanzee, yet K111 is not found in the genomes of other primates. Remarkably, K111 proviruses appear in the genomes of the extinct Neanderthal and Denisovan, while modern humans have at least 100 K111 proviruses spread across the centromeres of 15 chromosomes. Our studies suggest that the progenitor K111 integrated before the Homo-Pan divergence and expanded in copy number during the evolution of hominins, perhaps by recombination. The expansion of K111 provides sequence evidence suggesting that recombination between the centromeres of various chromosomes took place during the evolution of humans. K111 proviruses show significant sequence variations in each individual centromere, which may serve as markers in future efforts to annotate human centromere sequences. Further, this work is an example of the potential to discover previously unknown genomic sequences through the analysis of nucleic acids found in the blood of patients.

Best wishes,
OS.
 

anciendaze

Senior Member
Messages
1,841
I think there are two very interesting aspects of this work: the discovery of an entire family of HERV-K provirus which is novel; the techniques used to find HERVs which did not have precise sequence homology with previous known HERVs.

Now, I'm quite limited in my abilities, but I do have a mind which retains strange things like a magpie's nest. I seem to recall many other disease states which activate HERV-K: leukemia, renal and urethral carcinoma, breast cancer, melanoma, gonadalblastomas, ovarian cancer, chronic myeloid leukemia, rheumatoid arthritis, thrombocythemia, glioma, not to mention inflammatory brain diseases. HERV-K is the main HERV known to produce actual retroviral particles, and these appear to cause abnormal immune response in autoimmune diseases.

Now, obviously, I'm not depending on my highly fallible memory for these references, and I have not had time to read them carefully. Will others take a look, and tell us all which reports are completely independent of HIV infection? (Make that "known retroviral infection".)
 

Overstressed

Senior Member
Messages
406
Location
Belgium
Are you implying that retro/viruses might play a pathological role in human diseases? Autoimmune? Heresy! All diseases are genetic in origin, and happen by God's will. Amen.


We only know two retroviruses that could jump to humans, and that is...tataa:

HTLV and HIV

Which other retroviruses? Other retroviruses don't exist in humans :)

natasa778: I have to admit, your humor and cynicism is waaaaay much better than mine. You really made my day ;)

Best wishes,
OS.
 

anciendaze

Senior Member
Messages
1,841
The HERV-K progenitor sequence appears to have been a beta retrovirus. How about the 85% of ME/CFS patient samples which turned up with what appeared to be random gamma retroviral sequences in the Lo/Alter work, and apparently in the latest (unpublished) Lipkin work? Anyone interested in finding what triggered transcription?