Antiviral drug resistance of human cytomegalovirus.
Nell S. Lurain,Sunwen Chou +1 more
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TLDR
The virological and clinical data pertaining to HCMV antiviral drug resistance is summarized, which shows an evolving list of confirmed resistance mutations, although differences in interpretation have led to some confusion.Abstract:
Summary: The study of human cytomegalovirus (HCMV) antiviral drug resistance has enhanced knowledge of the virological targets and the mechanisms of antiviral activity. The currently approved drugs, ganciclovir (GCV), foscarnet (FOS), and cidofovir (CDV), target the viral DNA polymerase. GCV anabolism also requires phosphorylation by the virus-encoded UL97 kinase. GCV resistance mutations have been identified in both genes, while FOS and CDV mutations occur only in the DNA polymerase gene. Confirmation of resistance mutations requires phenotypic analysis; however, phenotypic assays are too time-consuming for diagnostic purposes. Genotypic assays based on sequencing provide more rapid results but are dependent on prior validation by phenotypic methods. Reports from many laboratories have produced an evolving list of confirmed resistance mutations, although differences in interpretation have led to some confusion. Recombinant phenotyping methods performed in a few research laboratories have resolved some of the conflicting results. Treatment options for drug-resistant HCMV infections are complex and have not been subjected to controlled clinical trials, although consensus guidelines have been proposed. This review summarizes the virological and clinical data pertaining to HCMV antiviral drug resistance.read more
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The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation
Camille N. Kotton,Deepali Kumar,Angela M. Caliendo,Shirish Huprikar,Sunwen Chou,Lara Danziger-Isakov,Atul Humar +6 more
TL;DR: Highlights include advances in molecular and immunologic diagnostics, improved understanding of diagnostic thresholds, optimized methods of prevention, advances in the use of novel antiviral therapies and certain immunosuppressive agents, and more savvy approaches to treatment resistant/refractory disease.
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TL;DR: Primary infection manifests as an asymptomatic or self-limited febrile illness in immunocompetent individuals, after which CMV establishes life-long latency in various cells, which serve as reservoirs for reactivation and as carriers of infection to susceptible individuals.
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Multidrug Resistance: An Emerging Crisis
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TL;DR: There is an increasing use of CMV‐specific cell‐mediated immune assays to stratify the risk ofCMV infection after solid organ transplantation, but their role in optimizing CMV prevention and treatment efforts has yet to be demonstrated.
References
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TL;DR: Phylogenetic mapping of the conserved protein kinase catalytic domains can serve as a useful first step in the functional characterization of these newly identified family members.
Journal ArticleDOI
The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation
Camille N. Kotton,Deepali Kumar,Angela M. Caliendo,Shirish Huprikar,Sunwen Chou,Lara Danziger-Isakov,Atul Humar +6 more
TL;DR: Highlights include advances in molecular and immunologic diagnostics, improved understanding of diagnostic thresholds, optimized methods of prevention, advances in the use of novel antiviral therapies and certain immunosuppressive agents, and more savvy approaches to treatment resistant/refractory disease.
Journal ArticleDOI
Simple and highly efficient BAC recombineering using galK selection
TL;DR: Three new recombineering strains are described that allow bacterial artificial chromosomes (BACs) to be modified using galK positive/negative selection, and it is shown how galK selection can be used to rapidly introduce point mutations, deletions and loxP sites into BAC DNA and thus facilitate functional studies of SNP and/or disease-causing point mutations.
Journal ArticleDOI
Seroprevalence of Cytomegalovirus Infection in the United States, 1988–1994
Stephanie A. S. Staras,Sheila C. Dollard,Kay Radford,W. Dana Flanders,Robert F. Pass,Michael J. Cannon +5 more
TL;DR: It is estimated that each year in the United States approximately 340,000 non-Hispanic white persons, 130,000non-Hispanic black persons, and 50,000 Mexican American women of childbearing age experience a primary CMV infection.
Antiretroviral Drug Resistance Testing in Adult HIV-1 Infection
Martin S. Hirsch,Scott M. Hammer,Victoria A. Johnson,Daniel R. Kuritzkes,Clive Loveday,John W. Mellors,Bonaventura Clotet,Brian Conway,Lisa M. Demeter,Stefano Vella,Donna M. Jacobsen,Douglas D. Richman +11 more
TL;DR: Emerging data indicate that despite limitations, resistance testing should be incorporated into patient management in some settings, and resistance testing is recommended to help guide the choice of new regimens after treatment failure and for guiding therapy for pregnant women.
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