Inhibition of XMRV by a weapon of mass deamination

Messages
235
Likes
45
Location
Teesside, England UK
Inhibition of XMRV by a weapon of mass deamination by Vincent Racaniello on 20th April 2010

Any science brains upto translating this article?

Inhibition of XMRV by a weapon of mass deamination by Vincent Racaniello on 20th April 2010

"All mammalian genomes contain genes encoding Apobec proteins. Several members of this protein family (the name stands for apolipoprotein B mRNA editing complex) are induced by interferon and are intrinsic antiretroviral proteins. Apobec proteins inhibit the replication of XMRV, a new human retrovirus associated with prostate cancer and chronic fatigue syndrome.

During retroviral replication, Apobec proteins are packaged into newly synthesized retrovirus particles (illustrated). They exert their antiviral effect when Apobec-containing virions infect a new cell. As the viral reverse transcriptase begins to copy viral RNA into DNA, Apobec removes an amine group from cytosines in single stranded DNA, a process called deamination. The consequence of deamination is that cytosine is changed to uracil. Uracil-containing DNA may be attacked by uracil DNA glycosidase, which removes the base and makes the DNA susceptible to degradation. If deaminated DNA is copied to form a double-stranded molecule, the new Us pair with As. In other words, deamination leads to a G-to-A mutation in the viral DNA. The highly mutated DNA cannot encode viable viruses, and the infection is terminated. For this reason one retrovirologist has called Apobec a WMD – a weapon of mass deamination.
Apobec is lethal for retroviruses that incorporate the enzyme into their virions. Human immunodeficiency virus-1 counters this defense by producing the Vif protein, which binds to Apobec and promotes its degradation by cellular enzymes.
XMRV does not encode a Vif protein and should be susceptible to inhibition by Apobec proteins. To answer this question, XMRV virions were produced in cells in the presence of different Apobec proteins. The deaminases were incorporated into virions, where they resulted in G-to-A hypermutation and inhibition of viral infectivity.
Could the presence of Apobec determine which human tissues are infected with XMRV? The virus replicates very well in a prostate cancer cell line, LNCaP, which produces reduced levels of Apobec proteins. Whether Apobec could regulate XMRV replication in the prostate is not known because expression of the protein in normal or malignant prostate tissues has not been studied. A conundrum which requires further investigation concerns the isolation of XMRV from CD4+ T and B cells, which are known to synthesize Apobec proteins. How XMRV might evade Apobec inhibition in these cells remains unexplained.

Paprotka, T., Venkatachari, N., Chaipan, C., Burdick, R., Delviks-Frankenberry, K., Hu, W., & Pathak, V. (2010). Inhibition of Xenotropic Murine Leukemia Virus-Related Virus by APOBEC3 Proteins and Antiviral Drugs Journal of Virology DOI: 10.1128/JVI.00134-10
Groom, H., Yap, M., Galao, R., Neil, S., & Bishop, K. (2010). Susceptibility of xenotropic murine leukemia virus-related virus (XMRV) to retroviral restriction factors Proceedings of the National Academy of Sciences, 107 (11), 5166-5171 DOI: 10.1073/pnas.0913650107
http://www.virology.ws/2010/04/20/inhibition-of-xmrv-by-a-weapon-of-mass-deamination/?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed:%20VirologyBlog%20%28virology%20blog%29"
 
G

Gerwyn

Guest

natasa778

Senior Member
Messages
1,774
Likes
2,447
Very interesting thanks, I wonder if something like this - differences in Apobec gene/s, could be one of reasons some can carry XMRV (or HIV) and not develop disease.

Here are several other papers:

APOBEC3 inhibits mouse mammary tumour virus replication in vivo
http://www.nature.com/nature/journal/v445/n7130/full/nature05540.html
... Genomes of all mammals encode apobec3 genes, which are thought to have a function in intrinsic cellular immunity to several viruses including HIV-1... However, the role of A3 in innate resistance to mouse retroviruses is not understood. Here we show that A3 functions during retroviral infection in vivo and provides partial protection to mice against infection with mouse mammary tumour virus (MMTV). Both mouse A3 and human A3G proteins interacted with the MMTV nucleocapsid in an RNA-dependent fashion and were packaged into virions. In addition, mouse A3-containing and human A3G-containing virions showed a marked decrease in titre. Last, A3-/- mice were more susceptible to MMTV infection, because virus spread was more rapid and extensive than in their wild-type littermates.

APOBEC3 proteins mediate the clearance of foreign DNA from human cells http://www.nature.com/nsmb/journal/v17/n2/full/nsmb.1744.html


Gerwyn or anyone, could Apobec (dys)function be in any way linked to abnormalities of Rnase L in CFS?
 

leaves

Senior Member
Messages
1,193
Likes
28
Heheh I was reading: inhibition of xmrv by a weapon of mass destruction.
Might be effective though... :)
 

Overstressed

Senior Member
Messages
406
Likes
140
Location
Belgium
Very interesting thanks, I wonder if something like this - differences in Apobec gene/s, could be one of reasons some can carry XMRV (or HIV) and not develop disease.
If I can remember correctly, long term HIV non-progressors have high expressions of APOBEC proteins, that control retrovirus infection. And yes, I assume the same mechanism will control XMRV.

OS.