scholarly journals Crystal structures of the reverse transcriptase-associated ribonuclease H domain of xenotropic murine leukemia-virus related virus

2012 ◽  
Vol 177 (3) ◽  
pp. 638-645 ◽  
Author(s):  
Dongwen Zhou ◽  
Suhman Chung ◽  
Maria Miller ◽  
Stuart F.J. Le Grice ◽  
Alexander Wlodawer
2011 ◽  
Vol 40 (1) ◽  
pp. 345-359 ◽  
Author(s):  
Tanyaradzwa P. Ndongwe ◽  
Adeyemi O. Adedeji ◽  
Eleftherios Michailidis ◽  
Yee Tsuey Ong ◽  
Atsuko Hachiya ◽  
...  

2012 ◽  
Vol 56 (4) ◽  
pp. 2048-2061 ◽  
Author(s):  
Karen A. Kirby ◽  
Bruno Marchand ◽  
Yee Tsuey Ong ◽  
Tanyaradzwa P. Ndongwe ◽  
Atsuko Hachiya ◽  
...  

ABSTRACTRNase H inhibitors (RNHIs) have gained attention as potential HIV-1 therapeutics. Although several RNHIs have been studied in the context of HIV-1 reverse transcriptase (RT) RNase H, there is no information on inhibitors that might affect the RNase H activity of other RTs. We performed biochemical, virological, crystallographic, and molecular modeling studies to compare the RNase H function and inhibition profiles of the gammaretroviral xenotropic murine leukemia virus-related virus (XMRV) and Moloney murine leukemia virus (MoMLV) RTs to those of HIV-1 RT. The RNase H activity of XMRV RT is significantly lower than that of HIV-1 RT and comparable to that of MoMLV RT. XMRV and MoMLV, but not HIV-1 RT, had optimal RNase H activities in the presence of Mn2+and not Mg2+. Using hydroxyl-radical footprinting assays, we demonstrated that the distance between the polymerase and RNase H domains in the MoMLV and XMRV RTs is longer than that in the HIV-1 RT by ∼3.4 Å. We identified one naphthyridinone and one hydroxyisoquinolinedione as potent inhibitors of HIV-1 and XMRV RT RNases H with 50% inhibitory concentrations ranging from ∼0.8 to 0.02 μM. Two acylhydrazones effective against HIV-1 RT RNase H were less potent against the XMRV enzyme. We also solved the crystal structure of an XMRV RNase H fragment at high resolution (1.5 Å) and determined the molecular details of the XMRV RNase H active site, thus providing a framework that would be useful for the design of antivirals that target RNase H.


FEBS Journal ◽  
2012 ◽  
Vol 279 (8) ◽  
pp. 1433-1444 ◽  
Author(s):  
Verónica Barrioluengo ◽  
Yi Wang ◽  
Stuart F. J. Le Grice ◽  
Luis Menéndez-Arias

2014 ◽  
Vol 47 (3) ◽  
pp. 302-306 ◽  
Author(s):  
Samara Tatielle Monteiro Gomes ◽  
Luciana Imbiriba ◽  
Rommel Rodriguéz Burbano ◽  
Artur Luiz da Costa Silva ◽  
Rosimar Neris Martins Feitosa ◽  
...  

2012 ◽  
Vol 93 (5) ◽  
pp. 915-924 ◽  
Author(s):  
Harriet C. T. Groom ◽  
Kate N. Bishop

In 2006, a new retrovirus was isolated from prostate cancer patient tissue. Named xenotropic murine leukemia virus-related virus (XMRV), this was potentially the third class of retrovirus to be pathogenic in humans. XMRV made a more dramatic impact on the wider scientific community, and indeed the media, in 2009 when it was reported to be present in a remarkably high proportion of patients with chronic fatigue syndrome as well as a significant, albeit smaller, proportion of healthy controls. The apparent strong link to disease and the fear of a previously unknown retrovirus circulating in the general population lead to a surge in XMRV research. Subsequent studies failed to find an association of XMRV with disease and, in most cases, failed to find the virus in human samples. In 2011, the case against XMRV and human disease strengthened, ending with several decisive publications revealing the origin of the virus and demonstrating contamination of samples. In this review, we outline the passage of research on XMRV and its potential association with disease from its isolation to the present day, where we find ourselves at the end of a turbulent story.


Retrovirology ◽  
2009 ◽  
Vol 6 (1) ◽  
pp. 92 ◽  
Author(s):  
Oliver Hohn ◽  
Hans Krause ◽  
Pia Barbarotto ◽  
Lars Niederstadt ◽  
Nadine Beimforde ◽  
...  

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