Endogenous and exogenous retrovirus recombination and relevance for xmrv in xand?

[natasa778]

I find this fascinating so posting here what I've come across, could be of interest as there has been some discussion on endogenous versus exogenous expression and pathology in CFS


Mobilization of endogenous retroviruses in mice after infection with an exogenous retrovirus
Thus, infection by an exogenous virus may result not only in recombination with endogenous sequences, but also in the mobilization of complete endogenous retrovirus genomes via pseudotyping within exogenous retroviral virions. We report that the infection of mice with an ecotropic virus results in pseudotyping of intact endogenous viruses that have not undergone recombination. The endogenous retroviruses infect and are integrated into target cell genomes and subsequently replicate and spread as pseudotyped viruses. The mobilization of endogenous retroviruses upon infection with an exogenous retrovirus may represent a major interaction of exogenous retroviruses with endogenous retroviruses and may have profound effects on the pathogenicity of retroviral infections
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2648265/?tool=pubmed


Generation of a tumorigenic milk-borne mouse mammary tumor virus by recombination between endogenous and exogenous viruses. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC191541/?tool=pubmed


Also in cats

Recombination between feline exogenous and endogenous retroviral sequences generates tropism for cerebral endothelial cells.
Chakrabarti R, et al Am J Pathol. 1994 Feb;144(2):348-58.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1887149/?tool=pubmed
The data suggested that at least one or more of the presumptive recombinant viruses could specifically infect CNS-derived endothelial cells. Using polymerase chain reaction and DNA sequencing strategies to amplify and analyze DNA fragments of the proviral SU region from cells infected with REC-selected viruses, we found the occurrence of a single recombinant in which two-thirds of the SU gene from the N-terminus of FeLV-C was replaced by the endogenous FeLV element. This recombinant virus, when molecularly cloned, should be useful in determining its potential in vivo neuropathogenicity.

Endogenous env elements: partners in generation of pathogenic feline leukemia viruses. Roy-Burman P. Virus Genes. 1995;11(2-3):147-61.


And birds:

Avian endogenous provirus (ev-3) env gene sequencing: implication for pathogenic retrovirus origination.
Tikhonenko AT, Virus Genes. 1990 Feb;3(3):251-8.

The avian endogenous env gene product blocks the surface receptor and, as a result, cells become immune to related exogenous retroviruses. On the other hand, the same sequence can be included in the pathogenic retrovirus genome,
Our interest in endogenous viruses is based on their ability to make cells resistant to exogenous retroviruses. Expression of their major envelope glycoprotein leads to cellular surface receptor blockage and imparts immunity to infection by the related leukemia retroviruses.



And back to mice and cats again

We have investigated the intracellular proteins synthesized in rat XC and feline kidney cells transfected with endogenous mouse mammary tumor virus (MMTV) proviral DNA. The endogenous provirus GR40, associated with the Mtv-8 locus, directs the synthesis of gag proteins indistinguishable from those found in MMTV-infected cells. The env precursor Pr73env and the mature gp52 proteins could not be detected in these cells. Instead an env-related protein of 68K is synthesized. In contrast to this endogenous provirus, a cloned exogenous proviral variant directs the synthesis of apparently normal env proteins upon transfection into the same cell lines. These results suggest that the env gene of the endogenous MMTV provirus GR40 is defective. The exogenous proviral variant is not expected to synthesize virus particles since it carries a rearrangement in the gag gene. In order to obtain an MMTV provirus capable of correctly expressing both gag and env functions, we have constructed a hybrid endogenous-exogenous provirus containing the 5' long terminal repeat (LTR)-gag of GR40 and the pol-env-3' LTR of the exogenous provirus. Upon transfection into feline kidney cells, this hybrid provirus directed the synthesis of apparently authentic gag and env proteins
Production of mouse mammary tumor virus upon transfection of a recombinant proviral DNA into cultured cells. Salmons B, et al Virology. 1985 Jul 15;144(1):101-14.


Last one on Moloney murine leukemia retrovirus http://www.ncbi.nlm.nih.gov/pmc/articles/PMC391997/?tool=pubmed

 

[Gerwyn]

I find this fascinating so posting here what I've come across, could be of interest as there has been some discussion on endogenous versus exogenous expression and pathology in CFS…


Mobilization of endogenous retroviruses in mice after infection with an exogenous retrovirus
… Thus, infection by an exogenous virus may result not only in recombination with endogenous sequences, but also in the mobilization of complete endogenous retrovirus genomes via pseudotyping within exogenous retroviral virions. We report that the infection of mice with an ecotropic virus results in pseudotyping of intact endogenous viruses that have not undergone recombination. The endogenous retroviruses infect and are integrated into target cell genomes and subsequently replicate and spread as pseudotyped viruses. The mobilization of endogenous retroviruses upon infection with an exogenous retrovirus may represent a major interaction of exogenous retroviruses with endogenous retroviruses and may have profound effects on the pathogenicity of retroviral infections
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2648265/?tool=pubmed


Generation of a tumorigenic milk-borne mouse mammary tumor virus by recombination between endogenous and exogenous viruses. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC191541/?tool=pubmed


Also in cats

Recombination between feline exogenous and endogenous retroviral sequences generates tropism for cerebral endothelial cells.
Chakrabarti R, et al Am J Pathol. 1994 Feb;144(2):348-58.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1887149/?tool=pubmed
The data suggested that at least one or more of the presumptive recombinant viruses could specifically infect CNS-derived endothelial cells. Using polymerase chain reaction and DNA sequencing strategies to amplify and analyze DNA fragments of the proviral SU region from cells infected with REC-selected viruses, we found the occurrence of a single recombinant in which two-thirds of the SU gene from the N-terminus of FeLV-C was replaced by the endogenous FeLV element. This recombinant virus, when molecularly cloned, should be useful in determining its potential in vivo neuropathogenicity.

Endogenous env elements: partners in generation of pathogenic feline leukemia viruses. Roy-Burman P. Virus Genes. 1995;11(2-3):147-61.


And birds:

Avian endogenous provirus (ev-3) env gene sequencing: implication for pathogenic retrovirus origination.
Tikhonenko AT, Virus Genes. 1990 Feb;3(3):251-8.

The avian endogenous env gene product blocks the surface receptor and, as a result, cells become immune to related exogenous retroviruses. On the other hand, the same sequence can be included in the pathogenic retrovirus genome,…
… Our interest in endogenous viruses is based on their ability to make cells resistant to exogenous retroviruses. Expression of their major envelope glycoprotein leads to cellular surface receptor blockage and imparts immunity to infection by the related leukemia retroviruses….



And back to mice and cats again

We have investigated the intracellular proteins synthesized in rat XC and feline kidney cells transfected with endogenous mouse mammary tumor virus (MMTV) proviral DNA. The endogenous provirus GR40, associated with the Mtv-8 locus, directs the synthesis of gag proteins indistinguishable from those found in MMTV-infected cells. The env precursor Pr73env and the mature gp52 proteins could not be detected in these cells. Instead an env-related protein of 68K is synthesized. In contrast to this endogenous provirus, a cloned exogenous proviral variant directs the synthesis of apparently normal env proteins upon transfection into the same cell lines. These results suggest that the env gene of the endogenous MMTV provirus GR40 is defective. The exogenous proviral variant is not expected to synthesize virus particles since it carries a rearrangement in the gag gene. In order to obtain an MMTV provirus capable of correctly expressing both gag and env functions, we have constructed a hybrid endogenous-exogenous provirus containing the 5' long terminal repeat (LTR)-gag of GR40 and the pol-env-3' LTR of the exogenous provirus. Upon transfection into feline kidney cells, this hybrid provirus directed the synthesis of apparently authentic gag and env proteins…
Production of mouse mammary tumor virus upon transfection of a recombinant proviral DNA into cultured cells. Salmons B, et al Virology. 1985 Jul 15;144(1):101-14.


Last one on Moloney murine leukemia retrovirus http://www.ncbi.nlm.nih.gov/pmc/articles/PMC391997/?tool=pubmed

Natasa could the recombinant leave the cell and be relpicative in its own right hybrids do occur as part of the intrinsic defence mechanism but this would be something different entiely

 

[natasa778]

I don't see why not, although speculative only as far as I'm aware.

the first link is esp interesting in that "..In this report, we present evidence that infection of mice by an exogenous virus results in the mobilization of complete endogenous retroviruses. This includes proviruses that are severely defective and possess large deletions, as well as proviruses that are full length. Furthermore, the transferred sequences are transcribed and packaged into virions released from the newly infected cells.""'

 

[natasa778]

Gerwyn there is an interesting review here http://www.retrovirology.com/content/6/S2/I2
...Endogenous Retroviruses (ERVs) are present in all higher eukaryotes where they represent a large fraction of the genomes (8% in humans, divided into about 100 families). They are remnants of ancestral infections by bona fide retroviruses that have infected the germline and have thereafter been transmitted in a Mendelian manner. Conversely, they are a reservoir from which new infectious retroviruses can arise via recombination.... (I could not find ppt)


this one is probably unrelated but interesting http://www.retrovirology.com/content/6/S2/I5 Emergence of novel retroviruses

 

[Gerwyn]

Gerwyn there is an interesting review here http://www.retrovirology.com/content/6/S2/I2
...Endogenous Retroviruses (ERVs) are present in all higher eukaryotes where they represent a large fraction of the genomes (8% in humans, divided into about 100 families). They are remnants of ancestral infections by bona fide retroviruses that have infected the germline and have thereafter been transmitted in a Mendelian manner. Conversely, they are a reservoir from which new infectious retroviruses can arise via recombination.... (I could not find ppt)


this one is probably unrelated but interesting http://www.retrovirology.com/content/6/S2/I5 Emergence of novel retroviruses

sure what especially caught my eye is that they referred to mulv as an endo when it isnt I am just wondering what terminology they are using Mulv is latent and insered into the DNA but it is not an endogenous virus.Endos are well known pseudogenes and we respond to environmental changes to a lrge extent by their gene regulation activity===I have never heard of a truly endogenous reto being infective.They can sometimes insert their proteins into an exogenous to make another serotype but this would be something special and frightening

 

[parvofighter]

PERVS, recombination, and risks re: organ transplantation

Fascinating discussion natasa and Gerwyn. Thanks!

For some more on this topic, see the thread on PERV's (Porcine endogenous retroviruses), and the transplant industry's concerns about recombination and synergism with XMRV. Thread: http://www.forums.aboutmecfs.org/sh...concerns-Retrovirology-journal&highlight=PERV

Since recombination can occur between viruses, and recombinants can exhibit synergism, recipients should be tested for XMRV before xenotransplantation.

In other words, it would appear that transplant experts ARE indeed concerned about recombinants being infective and pathological.