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Author, Editor(s)

Author(s):

Svicher, Valentina
Sing, Tobias
Santoro, Maria Mercedes
Forbici, Federica
Rodriguez- Barrios, Fátima
Bertoli, Ada
Beerenwinkel, Niko
Bellocchi, Maria Concetta
Gago, Federigo
d´Arminio Monforte, Antonella
Antinori, Andrea
Lengauer, Thomas
Ceccherini-Silberstein, Francesca
Perno, Carlo-Federico

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Not MPG Author(s):

Svicher, Valentina
Santoro, Maria Mercedes
Forbici, Federica
Rodriguez- Barrios, Fátima
Bertoli, Ada
Beerenwinkel, Niko
Bellocchi, Maria Concetta
Gago, Federigo
d´Arminio Monforte, Antonella
Antinori, Andrea
Ceccherini-Silberstein, F.
Perno, Carlo-Federico

BibTeX cite key*:

Lengauer2006d

Title

Title*:

Involvement of novel HIV-1 reverse transcriptase mutations in the regulation of resistance to nucleoside inhibitors

Journal

Journal Title*:

Journal of Virology

Journal's URL:

http://jvi.asm.org/

Download URL
for the article:

http://jvi.asm.org/cgi/reprint/80/14/7186?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=Sing%2C+Tobias&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

Language:

English

Publisher

Publisher's
Name:


Publisher's URL:


Publisher's
Address:


ISSN:


Vol, No, pp, Date

Volume*:

80

Number:

14

Publishing Date:

2006

Pages*:

7186-7198

Number of
VG Pages:


Page Start:


Page End:


Sequence Number:


DOI:


Note, Abstract, ©

Note:


(LaTeX) Abstract:

We characterized 16 additional mutations in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) whose role in drug resistance is still unknown by analyzing 1,906 plasma-derived HIV-1 subtype B pol sequences from 551 drug-naïve patients and 1,355 nucleoside RT inhibitor (NRTI)-treated patients. Twelve mutations positively associated with NRTI treatment strongly correlated both in pairs and in clusters with known NRTI resistance mutations on divergent evolutionary pathways. In particular, T39A, K43E/Q, K122E, E203K, and H208Y clustered with the nucleoside analogue mutation 1 cluster (NAM1; M41L+L210W+T215Y). Their copresence in this cluster was associated with an increase in thymidine analogue resistance. Moreover, treatment failure in the presence of K43E, K122E, or H208Y was significantly associated with higher viremia and lower CD4 cell count. Differently, D218E clustered with the NAM2 pathway (D67N+K70R+K219Q+T215F), and its presence in this cluster determined an increase in zidovudine resistance. In contrast, three mutations (V35I, I50V, and R83K) negatively associated with NRTI treatment showed negative correlations with NRTI resistance mutations and were associated with increased susceptibility to specific NRTIs. In particular, I50V negatively correlated with the lamivudine-selected mutation M184V and was associated with a decrease in M184V/lamivudine resistance, whereas R83K negatively correlated with both NAM1 and NAM2 clusters and was associated with a decrease in thymidine analogue resistance. Finally, the association pattern of the F214L polymorphism revealed its propensity for the NAM2 pathway and its strong negative association with the NAM1 pathway. Our study provides evidence of novel RT mutational patterns that regulate positively and/or negatively NRTI resistance and strongly suggests that other mutations beyond those currently known to confer resistance should be considered for improved prediction of clinical response to antiretroviral drugs.

URL for the Abstract:

http://jvi.asm.org/cgi/content/abstract/80/14/7186?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=Sing%2C+Tobias&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

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Access Level:

Public

Correlation

MPG Unit:

Max-Planck-Institut für Informatik



MPG Subunit:

Computational Biology and Applied Algorithmics

Audience:

Expert

Appearance:

MPII WWW Server, MPII FTP Server, MPG publications list, university publications list, working group publication list, Fachbeirat, VG Wort


BibTeX Entry:

@ARTICLE{Lengauer2006d,
AUTHOR = {Svicher, Valentina and Sing, Tobias and Santoro, Maria Mercedes and Forbici, Federica and Rodriguez- Barrios, F{\'a}tima and Bertoli, Ada and Beerenwinkel, Niko and Bellocchi, Maria Concetta and Gago, Federigo and d´Arminio Monforte, Antonella and Antinori, Andrea and Lengauer, Thomas and Ceccherini-Silberstein, Francesca and Perno, Carlo-Federico},
TITLE = {Involvement of novel HIV-1 reverse transcriptase mutations in the regulation of resistance to nucleoside inhibitors},
JOURNAL = {Journal of Virology},
YEAR = {2006},
NUMBER = {14},
VOLUME = {80},
PAGES = {7186--7198},
}


Entry last modified by Christine Kiesel, 05/08/2007
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Editor(s)
Ruth Schneppen-Christmann
Created
01/10/2007 09:36:17 AM
Revisions
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Editor(s)
Christine Kiesel
Christine Kiesel
Uwe Brahm
Uwe Brahm
Uwe Brahm
Edit Dates
08.05.2007 21:55:25
08.05.2007 21:46:48
2007-04-16 16:15:04
2007-04-16 16:13:49
2007-04-16 16:10:53
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