Novel thogotovirus associated with febrile illness and death, United States, 2014.

A previously healthy man from eastern Kansas, USA, sought medical care in late spring because of a history of tick bite, fever, and fatigue. The patient had thrombocytopenia and leukopenia and was given doxycycline for a presumed tickborne illness. His condition did not improve. Multiorgan failure developed, and he died 11 days after illness onset from cardiopulmonary arrest. Molecular and serologic testing results for known tickborne pathogens were negative. However, testing of a specimen for antibodies against Heartland virus by using plaque reduction neutralization indicated the presence of another virus. Next-generation sequencing and phylogenetic analysis identified the virus as a novel member of the genus Thogotovirus.

Localized chronic fibrosing vasculitis in a tattoo: a unique adverse tattoo reaction.

Decorative tattoos are associated with a variety of adverse cutaneous reactions. We describe a unique fibrosing vasculitic reaction to red tattoo ink. The histopathology was similar to that in localized chronic fibrosing vasculitis (LCFV), but sharply limited to sites of red tattoo ink injection and associated with florid verrucoid epidermal hyperplasia. LCFV has been described in a broad variety of slowly progressive disorders with a firm consistency such as erythema elevatum diutinum, plasma cell granuloma, granuloma faciale, and IgG4-associated sclerosing diseases. It has been hypothesized that LCFV is the result of maladaptive immune reaction with failure to clear the causative antigen. To the best of our knowledge, this is the first case of LCFV associated with tattoo. We speculate on the implications our case holds for the pathogenesis of LCFV.

Ribosomal RNA sequence analysis of Brucella infection misidentified as Ochrobactrum anthropi infection.

A Brucella isolate was identified from purulent material collected during a hip surgery. Two previous blood cultures from the same patient yielded Ochrobactrum anthropi. After rRNA sequencing, all the isolates were identified as Brucella species and subsequently serotyped as Brucella suis. Misidentification of Brucella species remains a problem with bacterial identification systems.

Respiratory Viruses: Influenza, RSV, and Adenovirus in Kidney Transplantation.

Although advances in immunosuppression and antimicrobial prophylaxis have led to improved patient and graft survival, respiratory viruses continue to be a common cause of morbidity and mortality in immunocompromised populations. We describe the clinical manifestations, diagnosis and treatment options for influenza, respiratory syncytial virus and adenovirus infection in the kidney transplant population.

Novel antiviral agents for respiratory viral infection in immunocompromised adults.

Respiratory viruses cause significant morbidity and mortality in immunocompromised populations such as stem cell transplant and solid organ transplant patients. Few viruses causing respiratory tract infection have an approved therapy, and many of the viruses have no therapeutic options at all. In this article, we describe novel agents under development for treatment options against several respiratory viruses.

Delayed RSV diagnosis in a stem cell transplant population due to mutations that result in negative polymerase chain reaction.

Respiratory syncytial virus (RSV) is a serious cause of morbidity and mortality in the adult hematopoietic stem cell transplant (HSCT) population. The timely diagnosis of RSV infection in this population is important for initiating therapy and instituting appropriate infection prevention measures. Molecular multiplex assays now offer increased sensitivity for a more accurate diagnosis. This study presents 5 cases of RSV infection in HSCT patients in which diagnosis was delayed due to false-negative results from a multiplex polymerase chain reaction (PCR) assay. The false-negative result was due to a single base-pair mutation in the RSV strain. These false results delayed the appropriate treatment of patients. This study shows that a combination of a multiplex PCR assay, viral antigen, and/or culture should be used to detect variants of RSV in patients and that multiplex respiratory viral assays should develop a more robust design that includes multiple genetic target per virus to prevent missing viruses that continue to have genetic variances.

Pro-oncogenic cell signaling machinery as a target for oncolytic viruses.

Viruses function in close harmony with the signaling machinery of their host. Upon exposure to the cell, a battery of viral products become engaged in boosting friendly signaling elements of the host or suppressing harmful ones. The efficiency of viral replication is indeed the biological outcome of this interaction between cellular and host signaling molecules. Oncolytic viruses, natural or man-made, follow the same set of rules of engagement. Pro-oncogenic cell signaling machinery, therefore, is undoubtedly the most important area influencing the development of the next generation of effective, specific and rationally designed oncolytic viruses. Ras signaling, with its central role in what is known today as molecular oncology, is an attractive topic for studying the behavior of viruses versus cancer cells and to develop strategies to target cancer cells on the basis of such platform. This work reviews the development of oncolytic herpes viruses capable of targeting Ras signaling pathway along with a few other examples of viruses which are developed to contain specificity for certain pro-oncogenic characteristics of their host cells.

The role of the ELAV homologue EXC-7 in the development of the Caenorhabditis elegans excretory canals.

The exc mutations of Caenorhabditis elegans alter the position and shape of the apical cytoskeleton in polarized epithelial cells. Mutants in exc-7 form small cysts throughout the tubular excretory canals that regulate organismal osmolarity. We have cloned the exc-7 gene, the closest nematode homologue to the neural RNA-binding protein ELAV. EXC-7 is expressed in the canal for a short time midway through embryogenesis. Cysts in exc-7 mutants do not develop until several hours later, beginning at the time of hatching. We find that the first larval period is when the canal completes the majority of its outgrowth, and adds new apical cytoskeleton at a rapid rate. Ultrastructural studies show that exc-7 mutant defects resemble loss of beta(H)-spectrin (encoded by sma-1) at the distal ends of the excretory canals. In addition, exc-7 mutants exhibit synergistic excretory canal defects with mutations in sma-1, and EXC-7 binds sma-1 mRNA. These data imply that EXC-7 protein may affect expression of sma-1 and other genes to effect proper development of the excretory canals.