Introduction:
Human cytomegalovirus is one of the causes of opportunist
infections in
immunocompromised patients, and is triggered by factors such as
state of
viral latency, weakened
immune responses, and development of
antiviral resistance to
ganciclovir, the only
drug offered by the
public health system in
Brazil to treat the
infection. The
goal of this study was to identify
mutations that may be associated with
antiviral resistance in
immunocompromised patients.
Methods:
Molecular
analysis was performed in 82
blood samples and subjected to genomic
DNA extraction by a
silica-based
method. Three sequences of the HCMV UL97
gene, which encodes a
phosphotransferase protein required for activation of
ganciclovir, were amplified by
polymerase chain reaction.
Pyrosequencing methods were applied to one external 2096-bp segment
DNA and two internal sequences between
nucleotides 1087 to 1828 to detect
mutations in this
gene.
Results:
Approximately 10% of sequences contained
mutations between
nucleotides 377 and 594, in conserved regions of the UL97
gene, leading to
amino acid changes. Eleven
coding mutations were identified, including changes leading to
amino acid substitutions, E596K and S604F, which were observed in 100% of samples and are described for the first
time in
Brazil. In addition, one
mutation (A594V) that is associated with
ganciclovir resistance was detected in a
kidney transplant patient.
Conclusions:
Further studies to detect
mutations associated with HCMV resistance to
antiviral drugs are required to demonstrate the need to increase the variety and availability of
drugs used to treat
viral infections in the
public health care system in
Brazil.