Contrasting effect of new HCMV pUL54 mutations on antiviral drug susceptibility: Benefits and limits of 3D analysis

2016 ◽  
Vol 129 ◽  
pp. 115-119 ◽  
Author(s):  
D. Andouard ◽  
M.-C. Mazeron ◽  
G. Ligat ◽  
A. Couvreux ◽  
C. Pouteil-Noble ◽  
...  
Keyword(s):  
Antiviral Drug ◽  
Drug Susceptibility ◽  
3D Analysis ◽  
Contrasting Effect ◽  
Antiviral Drug Susceptibility

scholarly journals Genomic signatures and antiviral drug susceptibility profile of A(H1N1)pdm09

2012 ◽  
Vol 53 (2) ◽  
pp. 140-144 ◽  
Author(s):  
Marta Tiago Gíria ◽  
Helena Rebelo de Andrade ◽  
Luís André Santos ◽  
Vanessa Martins Correia ◽  
Sónia Vicente Pedro ◽  
...  
Keyword(s):  
Antiviral Drug ◽  
Drug Susceptibility ◽  
Genomic Signatures ◽  
Antiviral Drug Susceptibility

scholarly journals Contrasting Effects of W781V and W780V Mutations in Helix N of Herpes Simplex Virus 1 and Human Cytomegalovirus DNA Polymerases on Antiviral Drug Susceptibility

2015 ◽  
Vol 89 (8) ◽  
pp. 4636-4644 ◽  
Author(s):  
Jocelyne Piret ◽  
Nathalie Goyette ◽  
Brian E. Eckenroth ◽  
Emilien Drouot ◽  
Matthias Götte ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Dna Polymerase ◽  
Dna Polymerases ◽  
Antiviral Drug ◽  
Drug Susceptibility ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
Antiviral Drug Susceptibility ◽  
Hsv 1

ABSTRACTDNA polymerases of theHerpesviridaeand bacteriophage RB69 belong to the α-like DNA polymerase family. In spite of similarities in structure and function, the RB69 enzyme is relatively resistant to foscarnet, requiring the mutation V478W in helix N to promote the closed conformation of the enzyme to make it susceptible to the antiviral. Here, we generated recombinant herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) mutants harboring the revertant in UL30 (W781V) and UL54 (W780V) DNA polymerases, respectively, to further investigate the impact of this tryptophan on antiviral drug susceptibility and viral replicative capacity. The mutation W781V in HSV-1 induced resistance to foscarnet, acyclovir, and ganciclovir (3-, 14-, and 3-fold increases in the 50% effective concentrations [EC50s], respectively). The recombinant HCMV mutant harboring the W780V mutation was slightly resistant to foscarnet (a 1.9-fold increase in the EC50) and susceptible to ganciclovir. Recombinant HSV-1 and HCMV mutants had altered viral replication kinetics. The apparent inhibition constant values of foscarnet against mutant UL30 and UL54 DNA polymerases were 45- and 4.9-fold higher, respectively, than those against their wild-type counterparts. Structural evaluation of the tryptophan position in the UL54 DNA polymerase suggests that the bulkier phenylalanine (fingers domain) and isoleucine (N-terminal domain) could induce a tendency toward the closed conformation greater than that for UL30 and explains the modest effect of the W780V mutation on foscarnet susceptibility. Our results further suggest a role of the tryptophan in helix N in conferring HCMV and especially HSV-1 susceptibility to foscarnet and the possible contribution of other residues localized at the interface between the fingers and N-terminal domains.IMPORTANCEDNA polymerases of theHerpesviridaeand bacteriophage RB69 belong to the α-like DNA polymerase family. However, the RB69 DNA polymerase is relatively resistant to the broad-spectrum antiviral agent foscarnet. The mutation V478W in helix N of the fingers domain caused the enzyme to adopt a closed conformation and to become susceptible to the antiviral. We generated recombinant herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) mutants harboring the revertant in UL30 (W781V) and UL54 (W780V) DNA polymerases, respectively, to further investigate the impact of this tryptophan on antiviral drug susceptibility. The W781V mutation in HSV-1 induced resistance to foscarnet, whereas the W780V mutation in HCMV slightly decreased drug susceptibility. This study suggests that the different profiles of susceptibility to foscarnet of the HSV-1 and HCMV mutants could be related to subtle conformational changes resulting from the interaction between residues specific to each enzyme that are located at the interface between the fingers and the N-terminal domains.

Guidance for clinical and public health laboratories testing for influenza virus antiviral drug susceptibility in Europe

2013 ◽  
Vol 57 (1) ◽  
pp. 5-12 ◽  
Author(s):  
Francisco Pozo ◽  
Bruno Lina ◽  
Helena Rebelo de Andrade ◽  
Vincent Enouf ◽  
Athanasios Kossyvakis ◽  
...  
Keyword(s):  
Public Health ◽  
Influenza Virus ◽  
Antiviral Drug ◽  
Drug Susceptibility ◽  
Antiviral Drug Susceptibility

Flow cytometric antiviral drug susceptibility assays

1999 ◽  
Vol 19 (1-2) ◽  
pp. 1-14
Author(s):  
James J. McSharry
Keyword(s):  
Antiviral Drug ◽  
Drug Susceptibility ◽  
Flow Cytometric ◽  
Antiviral Drug Susceptibility

Antiviral drug susceptibility assays: going with the flow

1999 ◽  
Vol 43 (1) ◽  
pp. 1-21 ◽  
Author(s):  
James J McSharry
Keyword(s):  
Antiviral Drug ◽  
Drug Susceptibility ◽  
Antiviral Drug Susceptibility

Rapid determination of antiviral drug susceptibility of herpes simplex virus types 1 and 2 by real-time PCR

2006 ◽  
Vol 69 (3) ◽  
pp. 152-157 ◽  
Author(s):  
T THI ◽  
C DEBACK ◽  
I MALET ◽  
P BONNAFOUS ◽  
Z AITARKOUB ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Real Time ◽  
Real Time Pcr ◽  
Rapid Determination ◽  
Antiviral Drug ◽  
Drug Susceptibility ◽  
Simplex Virus ◽  
Antiviral Drug Susceptibility

scholarly journals Application of Real-Time PCR for Determination of Antiviral Drug Susceptibility of Herpes Simplex Virus

2002 ◽  
Vol 46 (9) ◽  
pp. 2943-2947 ◽  
Author(s):  
Růžena Stránská ◽  
Anton M. van Loon ◽  
Merjo Polman ◽  
Rob Schuurman
Keyword(s):  
Herpes Simplex ◽  
Real Time ◽  
Real Time Pcr ◽  
Antiviral Drug ◽  
Drug Susceptibility ◽  
Pcr Assay ◽  
Simplex Virus ◽  
Antiviral Drug Susceptibility ◽  
Hsv 1

ABSTRACT A quantitative real-time PCR (TaqMan) assay was developed for determination of antiviral drug susceptibility of herpes simplex virus (HSV). After short-time culture of the virus, the antiviral drug susceptibility of HSV isolates for acyclovir (ACV) was determined by measuring the reduction of the HSV type 1 (HSV-1) DNA levels in culture supernatants using real-time PCR. The 50% inhibitory concentration was reported as the concentration of antiviral drug that reduced the number of HSV-1 DNA copies by 50%. A total of 15 well-characterized ACV-sensitive or -resistant strains and clinical isolates were used for assay evaluation. The new assay with real-time PCR readout permitted rapid (3 days), objective, and reproducible determination of HSV-1 drug susceptibilities with no need for stringent control of initial multiplicity of infection. Furthermore, the real-time PCR assay results showed good correlation (r = 0.86) with those for the plaque reduction assay. In conclusion, the real-time PCR assay described here is a suitable quantitative method for determination of antiviral susceptibility of HSV-1, amenable for use in the routine diagnostic virology laboratory.

Real-time PCR determination of human herpesvirus 6 antiviral drug susceptibility

2007 ◽  
Vol 140 (1-2) ◽  
pp. 25-31 ◽  
Author(s):  
Yuji Isegawa ◽  
Masaya Takemoto ◽  
Koichi Yamanishi ◽  
Atsushi Ohshima ◽  
Nakaba Sugimoto
Keyword(s):  
Real Time ◽  
Real Time Pcr ◽  
Antiviral Drug ◽  
Human Herpesvirus ◽  
Drug Susceptibility ◽  
Human Herpesvirus 6 ◽  
Herpesvirus 6 ◽  
Antiviral Drug Susceptibility

Amino acid insertions at position 35 of HIV-1 protease interfere with virus replication without modifying antiviral drug susceptibility

2006 ◽  
Vol 69 (3) ◽  
pp. 181-185 ◽  
Author(s):  
S PAOLUCCI ◽  
F BALDANTI ◽  
L DOSSENA ◽  
G GERNA
Keyword(s):  
Amino Acid ◽  
Virus Replication ◽  
Antiviral Drug ◽  
Drug Susceptibility ◽  
Hiv 1 ◽  
Antiviral Drug Susceptibility
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