explain this? "BIOCHEMICAL, STRUCTURAL, INHIBITION STUDIES OF XMRV REVERSE TRANSCRIPT

RivkaRivka

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Can anyone explain to me what this paper means??? - Best, Rivka
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http://antiviralresistance.org/abstr...ster5_2010.pdf

POSTER 5

BIOCHEMICAL, STRUCTURAL, AND INHIBITION STUDIES OF XMRV REVERSE TRANSCRIPTASE

Tanya Ndognwe1, Karen Kirby1, Bruno Marchand1, Adeyemi Adedeji1,
Eleftherios Michailidis1, Yee-Tsuei Ong1, Atsuko Hachiya1, Emily
Ryan1, Shun-Lu Liu1, Angela Whatley1, Donald H. Burke1, Sanath Kumar1,
Marc Johnson1, Ei-Ichi Kodama2, Krista A. Delviks-Frankenberry3, Vinay
K. Pathak3, Hiroaki Mitsuya4, Michael A. Parniak5, Kamal Singh1, and
Stefan G. Sarafianos1

1Department of Molecular Microbiology & Immunology, University of
Missouri School of Medicine, Columbia, MO; 2Division of Emerging
Infectious Diseases, Tohoku University School of Medicine, Sendai,
Japan; 3HIV Drug Resistance Program, National Cancer Institute,
Frederick, MD; 4Department of Internal Medicine, Kumamoto University
School of Medicine, Kumamoto, Japan & Experimental Retrovirology
Section, HIV/AIDS Malignancy Branch, NIH, Bethesda, MD; 5Department of
Molecular Genetics & Biochemistry, University of Pittsburgh School of
Medicine, Pittsburgh, PA

The Xenotropic Murine Leukemia Virus-Related Virus (XMRV) was
originally identified in biological samples from familial prostate
cancer patients and was more recently reported in patients with
chronic fatigue syndrome (CFS). Although other studies have failed to
detect XMRV in CFS or prostate cancer patients, given the potential
importance of this virus for human disease we initiated studies on its
replication mechanism and susceptibility to inhibitors. We used
biochemical, biophysical, virological, and structural methods to
characterize the DNA polymerase and RNase H functions of XMRV reverse
transcriptase (RT). We compared the properties of XMRV RT, XMRV RNase
H, Moloney Murine Leukemia Virus (MuLV) RT, and HIV RT. Using steady
state and pre-steady state kinetics we demonstrated that XMRV RT is
the slowest and least efficient of the three enzymes in synthesizing
DNA or cleaving RNA/DNA. Similarly, its ability to unblock
chain-terminated primers using PPi or ATP are much lower compared to
HIV RT. Its reduced polymerase and RNAse H activity is due in part to
a lower affinity for nucleic acid, as judged by gel-shift assays and
confirmed by surface plasmon resonance experiments, which revealed
that the deficiency in DNA binding is due to a high dissociation rate.
Trap experiments showed that XMRV RT has very low processivity
compared to HIV RT. Transient kinetics of mismatch incorporations
revealed that XMRV RT has higher fidelity than MuLV and HIV RTs.
Nonetheless, XMRV and MuLV appear to have comparable fidelities in
cell-based assays. The polymerase function of XMRV RT is susceptible
to antiretrovirals from several classes, but not to NNRTIs. XMRV RT is
inhibited efficiently by AZT-TP, PMEADP, d4T-TP, PMPA-DP, and by a
nucleic acid aptamer. Two potent NRTIs that block XMRV RT efficiently
by a different mechanism also have potent antiviral activity in
pseudotype-based and replication competent virus-based assays. We have
also identified compounds that efficiently block the RNase H activity
of XMRV RT and of active XMRV RNase H fragments. Finally, we have
solved the crystal structure of XMRV RNase H at high resolution (1.5
), which will facilitate the design of new and more potent XMRV
inhibitors.
 

urbantravels

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It's technical stuff about the way reverse transcriptase (the enzyme that allows the RNA in a retrovirus to "copy" itself into DNA) works in XMRV. Blocking the action of reverse transcriptase is one of the ways that HIV drug "cocktails" work to suppress replication of the virus.

I'm not knowledgeable enough to say for sure, but it doesn't appear that the information in this study would cast any light on either detection or pathogenesis - it's just information that might ultimately help identify or develop drugs to treat XMRV.