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1.
J Virol ; 89(21): 11144-9, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26269192

ABSTRACT

Kaposi's sarcoma (KS) is common in Africa, but economic constraints hinder successful treatment in most patients. Propranolol, a generic ß-adrenergic antagonist, decreased proliferation of KS-associated herpesvirus (KSHV)-infected cells. Downregulation of cyclin A2 and cyclin-dependent kinase 1 (CDK1) recapitulated this phenotype. Additionally, propranolol induced lytic gene expression in association with downregulation of CDK6. Thus, propranolol has diverse effects on KSHV-infected cells, and this generic drug has potential as a therapeutic agent for KS.


Subject(s)
Adrenergic beta-Antagonists/pharmacology , Cell Proliferation/drug effects , Endothelial Cells/virology , Gene Expression Regulation, Neoplastic/drug effects , Herpesvirus 8, Human/metabolism , Propranolol/pharmacology , Sarcoma, Kaposi/drug therapy , CDC2 Protein Kinase , Cyclin A2/metabolism , Cyclin-Dependent Kinases/metabolism , Endothelial Cells/drug effects , Humans
2.
PLoS One ; 10(3): e0118529, 2015.
Article in English | MEDLINE | ID: mdl-25799541

ABSTRACT

Enterovirus D68 (EV-D68) is an emerging virus known to cause sporadic disease and occasional epidemics of severe lower respiratory tract infection. However, the true prevalence of infection with EV-D68 is unknown, due in part to the lack of a rapid and specific nucleic acid amplification test as well as the infrequency with which respiratory samples are analyzed by enterovirus surveillance programs. During the 2014 EV-D68 epidemic in the United States, we noted an increased frequency of "low-positive" results for human rhinovirus (HRV) detected in respiratory tract samples using the GenMark Diagnostics eSensor respiratory viral panel, a multiplex PCR assay able to detect 14 known respiratory viruses but not enteroviruses. We simultaneously noted markedly increased admissions to our Pediatric Intensive Care Unit for severe lower respiratory tract infections in patients both with and without a history of reactive airway disease. Accordingly, we hypothesized that these "low-positive" RVP results were due to EV-D68 rather than rhinovirus infection. Sequencing of the picornavirus 5' untranslated region (5'-UTR) of 49 samples positive for HRV by the GenMark RVP revealed that 33 (67.3%) were in fact EV-D68. Notably, the mean intensity of the HRV RVP result was significantly lower in the sequence-identified EV-D68 samples (20.3 nA) compared to HRV (129.7 nA). Using a cut-off of 40 nA for the differentiation of EV-D68 from HRV resulted in 94% sensitivity and 88% specificity. The robust diagnostic characteristics of our data suggest that the cross-reactivity of EV-D68 and HRV on the GenMark Diagnostics eSensor RVP platform may be an important factor to consider in making accurate molecular diagnosis of EV-D68 at institutions utilizing this system or other molecular respiratory platforms that may also cross-react.


Subject(s)
Enterovirus Infections/diagnosis , Enterovirus/isolation & purification , Picornaviridae Infections/diagnosis , Respiratory Tract Infections/virology , Rhinovirus/isolation & purification , Sequence Homology , 5' Untranslated Regions , Animals , Cell Line , Cross Reactions , Enterovirus/classification , Enterovirus/genetics , Enterovirus Infections/genetics , Enterovirus Infections/virology , Humans , Macaca mulatta , Multiplex Polymerase Chain Reaction , Pathology, Molecular , Picornaviridae Infections/genetics , Picornaviridae Infections/virology , Primary Cell Culture , Prognosis , Respiratory Tract Infections/epidemiology , Rhinovirus/genetics
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