Journal of Clinical Virology - Volume 82 - Supplement 1 - September 2016

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Abstracts / Journal of Clinical Virology 82S (2016) S1–S142 S17
and gamma on the Dunlop strain of BKV in Vero cells and 293FT
cells. Treatment with IFN-gamma inhibited the expression of the
viral late protein VP1 in a dose-dependent manner and decreased
the expression of the early and late viral transcripts. A weaker
antiviral effect was observedwith IFN-alpha and IFN-lambda. These
results are associated with a prolonged STAT1 phosphorylation
with IFN-gamma but not with IFN-alpha and lambda. The differ-
ence of efficacy between these two types of interferon suggests that
some interferon induced proteins, only produced by IFN-gamma
had an antiviral effect on BKV infection. Transcriptome analysis
reveals that six proteins could be involved in this specific antiviral
effect and are under investigation.
In conclusion, the most potent IFN on BKV infection is the IFN-
gamma. Finding the action mechanism of this effect could help to
develop a therapeutic strategy.
Abstract no: 231
Presentation at ESCV 2016: Oral 30
High incidence of gancliclovir-resistant
cytomegalovirus infections in solid organ
transplant patients
Hubert G.M. Niesters ∗, Danielle de Voogd ,
Sylvia Smit etta C. Van Leer-Buter
1 University Medical Center Groningen, University of
Groningen, Department of Medical Microbiology,
Division of Clinical Virology, The Netherlands
2 UMC Groningen, The Netherlands
Introduction: Human cytomegalovirus (CMV) is a pathogen
in immunocompromized individual such as recipients of solid
organ transplants. These patients aremonitored for CMV-DNAemia,
i.e. the presence of DNA in plasma, and treated when CMV
becomes detectable or when symptoms of CMV disease occur.
CMV-seronegative recipients of organs from CMV-seropositive
donors have a very high risk of developing CMV infections. CMV-
seropositive recipients may develop reactivations, or possibly
reinfections.
First line treatment of CMV infections is intravenous gancicolvir
or oral valgancicolvir. Studies have shown that antiviral resistance
may develop in up to 10% of treated individuals (Chou et al., 1999).
Resistance testing should be performed when there is doubt about
treatment response. This is usually done by sequencing the targets
for ganciclovir, the protein kinase and the viral polymerase gene,
UL54. In this study we determined how frequently CMV resistance
occurred in our hospital, which is the largest organ transplantation
center in the Netherlands.
Methods: Stored plasma samples of patients with CMV
DNAemia were retrospectively investigated for antiviral resistance
by sequencing the UL97 and UL54 genes. All patients who had
DNAemia at levels >10 000 copies/ml plasma for more than 2weeks
were included. Sequencing was performed according to methods
described before (Scott et al., 2004).
Results: 35 patients undergoing treatment for CMV disease
were included with a median of 3 samples per patient (range
2–9). In 13 (37%) patients with mutations were detected known
to be associated with resistance. In 12 (34%) patients no muta-
tions were detected. In 10 (29%) patients mutations were detected
which were not previously described. Resistance associated muta-
tions occurred more frequently in patients with high levels of
CMVDNA (>100 000 copies/ml) (P = 0.005). High levels of CMV-DNA
were more frequently observed during primary CMV infections.
Conclusions: Our research shows that in patients with CMV
DNA levels of >10 000 copies, the incidence of antiviral resistance
is nearly 40%. Further research with a larger number of patients
is needed to investigate factors associated with a higher risk of
developing antiviral resistance.
Abstract no: 116
Presentation at ESCV 2016: Oral 31
A multidrug resistant HSV1 infection occurring
under cidofovir treatment for ADV infection in
an immunocompromised child: Perspectives to
new antiviral drugs
L. Panetta ∗, V. Escuret , K. Michaux ,
G. Billaud ina orfi robert
1 Hospices Civils de Lyon, Institut d’Hématologie et
d’Oncologie Pédiatrique, Lyon, France
2 Hospices Civils de Lyon, Laboratoire de Virologie,
Institut des Agents Infectieux, UCBL CIRI INSERM
U1111, Virologie et Pathologie Humaine, Faculté de
Médecine RTH Laënnec, Lyon, France
3 Hospices Civils de Lyon, Laboratoire de Virologie,
Institut des Agents Infectieux, France
Resistance of herpes simplex viruses (HSV) to conventional
antiviral drugs acyclovir (ACV) and foscarnet (FOS) are an increasing
concern in immunocompromised patients and particularly bone
marrow transplant patients. Research in antiviral drugs leads to the
emergence of new therapeutic classes, as inhibitors of the helicase-
primase complex (HPI), pritelivir or amenamevir (Burrel et al.,
2014; Tyring et al., 2012). These new molecules represent poten-
tial optional treatment for herpes infections even for combination
therapy due to synergistic effect when used with ACV (reviewed in
James and Prichard, 2014).
We report a 16-year-old immunocompromised adolescent diag-
nosed with an acute myeloid leukemia (LAM2, FAB classification).
He had an infection with a systemic adenovirus (ADV) and pre-
sented a period of 5 months of aplasia after chemotherapy and
ADV infection. He underwent allogeneic hematopoietic stem cell
transplantation (HSCT). The HSV1 infection was firstly located at
mucocutaneous site with a voluminous lower lip lesion, then fol-
lowed by a systemic infectionwith a viral load up to 5100 copies/ml.
During the same period, the patient developped an ADV and BK
virus co infection. He received intravenous ACVand cidofovir (CDV),
associated with intravesical CDV. Sequence analysis of the full-
length UL23 encoding thymidine kinase gene, UL30 encoding DNA
polymerase gene and UL5 encoding helicase gene were performed.
No mutation was found on UL23 and UL5. Unfortunately, S724N
located on UL30 gene, known to confer multi resistance to ACV,
FOS and CDV was detected. In regards to this multidrug-resistant
strain, an authorisation for amenamevir use was also requested
and accepted by the French ANSM. The clinical evolution of the
HSV disease was favourable, as the lower lip lesion regressed and
the blood PCR HSV1 became negative. Nevertheless, this young
immunocompromised patient finally died from a multiple organ
failure.
Current treatment strategies lead to expose regularly immuno-
compromised patients to antiviral treatments. The selection of
multidrug-resistant strains could be explained by the circum-
stances of antiviral overexposure, used even for other viral
infection. Newantiviral drugs are deeply needed in order tomanage